The present invention relates to modified amino acids of general formula 
their tautomers, their diastereomers, their enantiomers, their mixtures and salts thereof, particularly physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them.
In the above general formula I
R denotes an unbranched C1-7-alkyl group which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or biphenylyl group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-2H-2-oxoimidazopyridinyl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl group, wherein the latter two groups may each be mono- or disubstituted in the 4- and/or 5-position or in the 5- and/or 6-position by lower straight chained or branched alkyl groups, by phenyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl-1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl groups and the substituents may be identical or different,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom, which contains one, two or three nitrogen atoms,
whilst a 1,4-butadienylene group may be attached both to the above-mentioned 5-membered heteroaromatic monocyclic rings and to the 6-membered heteroaromatic monocyclic rings, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
an unbranched C1-6-alkylamino group optionally substituted at the nitrogen atom by a C1-6-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl- or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl-group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom, containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl and alkylamino groups in the xcfx89-position and optionally also partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms or by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, wherein the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group, or the group of formula 
xe2x80x83wherein
p denotes the number 1 or 2,
o denotes the number 2 or 3 or, if Y1 and Y2 are not simultaneously nitrogen atoms, o may also denote 1.
Y1 denotes the nitrogen atom if R5 is a free pair of electrons, or the carbon atom,
Y2 is the nitrogen atom or the group  greater than CHxe2x80x94,
R5 is a free pair of electrons if Y1 denotes the nitrogen atom or, if Y1 denotes the carbon atom, R5 denotes a hydrogen atom, a C1-3-alkyl group, a hydroxy, cyano, aminocarbonyl, carboxy, alkoxycarbonyl, aminocarbonylamino, phenylmethyl or phenyl group,
R6 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom, R6 together with R5 may denote an additional bond,
R7 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom and R5 and R6 together constitute an additional bond, R7 together with RN may also denote a 1,4-butadienylene group,
RN denotes a hydrogen atom or a C1-6-alkyl group which may be mono- or disubstituted in the xcfx89-position
by a C5-7-cycloalkyl group, by a 1-naphthyl, 2-naphthyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, piperidinyl, morpholinyl, pyrrolidinyl, hexahydro-1H-1-azepinyl, aminocarbonyl, alkylaminocarbonyl, acetylamino, cyano, aminocarbonylamino or alkylaminocarbonylamino group or by phenyl, pyridinyl or diazinyl groups, whilst these substituents may be identical or different,
a C5-7-cycloalkyl group, a phenyl, pyridinyl, cyano, amino, benzoylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonyl, phenylalkoxycarbonyl, aminocarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, N-(aminocarbonyl)-N-alkylamino, N-(alkylaminocarbonyl)-N-alkylamino, N-(alkylaminocarbonyl)-N-phenylamino, phenylaminocarbonylamino, [phenyl(alkylamino)]carbonylamino, N-(phenylaminocarbonyl)-N-alkylamino, N-(phenylaminocarbonyl)-N-phenylamino, benzoylaminocarbonylamino, phenylalkylaminocarbonylamino, pyridinylaminocarbonylamino, N-(aminocarbonyl)-N-phenylamino, N-(alkylaminocarbonyl)-N-phenylamino, N-(aminocarbonylaminocarbonyl)-N-phenylamino, N-(pyridinyl)-N-(aminocarbonyl)amino, N-(pyridinyl)-N-(alkylaminocarbonyl)amino, phenylamino, pyridinylamino, 4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl or diazinylamino group,
a saturated, mono- or di-unsaturated 5- to 7-membered aza, diaza, triaza, oxaza, thiaza, thiadiaza- or S,S-dioxido-thiadiaza-heterocycle.
wherein the above-mentioned heterocycles may be linked via a carbon or nitrogen atom and
may contain one or two carbonyl groups adjacent to a nitrogen atom,
may be substituted at one of the nitrogen atoms by an alkyl, alkanoyl, aroyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, phenylalkoxycarbonylalkyl, phenylmethyl or phenyl group,
may be substituted at one or two carbon atoms by a branched or unbranched alkyl group or by a phenyl, phenylmethyl, naphthyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl group, wherein the substituents may be the same or different,
and wherein a C3-6-alkylene group may additionally be attached to the above-mentioned heterocycles via two adjacent carbon atoms or an olefinic double bond of one of the above-mentioned unsaturated heterocycles may be fused with a benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methyl-pyrrole, quinoline, imidazole or N-methylimidazole ring,
or if Y1 is not a nitrogen atom and R5 and R6 together denote an additional bond, RN together with R7 may also denote the 1,4-butadienylene group,
or, if Y1 is a carbon atom, RN together with R5, including Y1, also denotes a carbonyl group or a saturated or mono-unsaturated 5- or 6-membered 1,3-diaza-heterocycle which may optionally contain one or two carbonyl groups in the ring and, if it is unsaturated, may be benzofused at the double bond and may be substituted at one of the nitrogen atoms by a methyl, aminocarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, phenylalkoxycarbonylalkyl, phenylmethyl or phenyl group,
whilst the phenyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl- or 1-methylimidazolyl groups contained in the residues mentioned under R5, R7 and RN, as well as benzo, thieno, pyrido- and diazino-fused heterocycles in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulphonylamino, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxyalkylaminocarbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino, aminocarbonylaminoalkyl, alkylaminocarbonylamino, alkanoyl, cyano, trifluoromethoxy, trifluormethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, wherein the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino, benzoylaminocarbonylamino and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino- or acetylamino group
and unless otherwise specified the alkyl groups contained in the above-mentioned radicals may contain 1 to 5 carbon atoms,
X denotes an oxygen atom or 2 hydrogen atoms,
Z denotes a methylene group or the group xe2x80x94NR1, wherein
R1 denotes a hydrogen atom or an alkyl or phenylalkyl group,
R11 denotes a hydrogen atom, a C1-3-alkyl group, an alkoxycarbonyl group having a total of 2 to 4 carbon atoms or a phenylmethyl group,
n denotes the number 1 or 2 or, if m is 1, n may also be 0,
m denotes the number 0 or 1,
R2 denotes a phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydro-1-naphthyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yl, 1-(1,1-dimethylethoxycarbonyl)-1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 2-thienyl, 3-thienyl, thiazolyl, 1H-indazol-3-yl, 1-methyl-1H-indazol-3-yl, benzo[b]fur-3-yl, benzo[b]thien-3-yl, pyridinyl, qui-nolinyl or isoquinolinyl group,
whilst the above-mentioned aromatic and heteroaromatic groups in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms or by branched or unbranched alkyl groups, C3-8-cycloalkyl groups, phenylalkyl groups, alkenyl, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonylalkyl, carboxyalkyl, alkoxycarbonyl, carboxy, dialkylaminoalkyl, dialkylaminoalkoxy, hydroxy, nitro, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, methylsulphonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, tetrazolyl, phenyl, pyridinyl, thiazolyl, furyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, and the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom, or by an alkyl, trifluoromethyl, amino or acetylamino group,
A denotes a bond or the divalent group of formula 
(which is linked to the NR3R4 group via the xe2x80x94CX group)
xe2x80x83wherein
R8 and R9 together denote an n-propylene group or
R8 denotes a hydrogen atom or an alkyl- or phenylalkyl group and
R9 denotes a hydrogen atom or a branched or unbranched C1-5-alkyl group which, if it is unbranched, may be substituted in the xcfx89-position by a hydroxy, mercapto, amino, alkylamino, dialkylamino, 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, hexahydro-1-azepinyl, methylthio, hydroxycarbonyl, aminocarbonyl, aminoiminomethylamino, aminocarbonylamino, phenyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 1-naphthyl, 2-naphthyl- or pyridinyl group, whilst the above-mentioned heterocycles, phenyl and naphthyl groups may in turn be mono-, di- or trisubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms or by methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, trifluoromethoxy, methylsulphonyloxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, wherein the substituents may be identical or different, and wherein the hydroxy, mercapto, amino, guanidino, indolyl and imidazolyl groups contained in the groups mentioned for R9 may be substituted with the protecting groups commonly used in peptide chemistry, preferably with the acetyl, benzyloxycarbonyl or tert.butyloxycarbonyl group,
R3 denotes a hydrogen atom,
a C1-7-alkyl group which may be substituted in the xcfx89-position by a cyclohexyl, phenyl, pyridinyl, diazinyl, hydroxy, amino, alkylamino, dialkylamino, carboxy, aminocarbonyl, aminocarbonylamino, acetylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-(1-piperidinyl)-1-piperidinyl, 4-morpholinyl, hexahydro-1H-1-azepinyl, [bis-(2-hydroxyethyl)]amino, 4-alkyl-1-piperazinyl or 4-(xcfx89-hydroxyalkyl)-1-piperazinyl group,
a phenyl or pyridinyl group,
wherein the above-mentioned heterocyclic groups and phenyl groups may additionally be mono-, di- or trisubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms or by methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, methylsulphonyloxy, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups and the substituents may be identical or different,
R4 denotes a hydrogen atom or a C1-3-alkyl group optionally substituted by a phenyl or pyridinyl group or
R3 and R4 together with the enclosed nitrogen atom denote a group of general formula 
xe2x80x83wherein
Y3 denotes a carbon atom or, if R12 denotes a free pair of electrons, Y3 may also be the nitrogen atom,
r denotes the number 0, 1 or 2,
q denotes the number 0, 1 or 2,
R10 denotes a hydrogen atom or an amino, alkylamino, dialkylamino, alkyl, cycloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminoiminomethyl, aminocarbonylamino, alkylaminocarbonylamino, cycloalkylaminocarbonylamino, phenylaminocarbonylamino, aminocarbonylalkyl, aminocarbonylaminoalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxyalkyl or carboxy group,
a phenyl, pyridinyl, diazinyl, 1-naphthyl, 2-naphthyl, pyridinylcarbonyl- or phenylcarbonyl-group which may be mono-, di- or trisubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms, or by alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylaminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, xcfx89-(dialkylamino)alkanoyl, xcfx89-(dialkylamino)alkyl, xcfx89-(dialkylamino)hydroxyalkyl, xcfx89-(carboxy)alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different,
a 1,3-dihydro-2-oxo-2H-imidazolyl, 2,4(1H,3H)-dioxopyrimidinyl or 3,4-dihydro-2(1H)-oxopyrimidinyl group bound via a nitrogen atom, which may be substituted by a phenyl group or fused at the double bond to a benzene, pyridine or diazine ring,
a 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl group,
a 4- to 10-membered azacycloalkyl group, a 5- to 10-membered oxaza, thiaza- or diazacycloalkyl group or a 6- to 10-membered azabicycloalkyl group,
wherein the above-mentioned mono- and bicyclic heterocycles may be bound via a nitrogen or carbon atom and
may be substituted by a C1-7-alkyl group, by an alkanoyl, dialkylamino, phenylcarbonyl, pyridinylcarbonyl, carboxyalkanoyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylsulphonyl, cycloalkyl- or cycloalkylalkyl group, by a cycloalkylcarbonyl, azacycloalkylcarbonyl, diazacycloalkylcarbonyl or oxazacycloalkylcarbonyl group optionally substituted in the ring,
whilst the alicyclic parts contained in these substituents may comprise 3 to 10 ring members and the heteroalicyclic parts may comprise 4 to 10 ring members and
the above-mentioned phenyl and pyridinyl groups may in turn be mono- , di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylaminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, xcfx89-(dialkylamino)alkanoyl, xcfx89-(carboxy)alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different, or
R10 together with R12 and Y3 denotes a 4- to 7-membered cycloaliphatic ring in which a methylene group may be replaced by an xe2x80x94NHxe2x80x94 or xe2x80x94N(alkyl)xe2x80x94 group,
whilst a hydrogen atom bound to a nitrogen atom within the group R10 may be replaced by a protecting group,
R12 denotes a hydrogen atom,
a C1-4-alkyl group, wherein an unbranched alkyl group may be substituted in the co-position by a phenyl, pyridinyl, diazinyl, amino, alkylamino, dialkylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-methyl-1-piperazinyl, 4-morpholinyl- or hexahydro-1H-1-azepinyl group,
an alkoxycarbonyl, cyano or aminocarbonyl group or a free pair of electrons, if Y3 denotes a nitrogen atom, and
R13 and R14 in each case denote a hydrogen atom or,
if Y3 is a carbon atom, R12 together with R14 also denotes another carbon-carbon bond, wherein R10 is as hereinbefore defined and R13 denotes a hydrogen atom or
if Y3 is a carbon atom, R12 together with R14 also denotes another carbon-carbon bond and R10 together with R13 and the enclosed double bond denotes a partially hydrogenated or aromatic 5- to 7-membered mono- or bicyclic carbocycle or heterocycle,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 7 carbon atoms, unless otherwise specified,
all the above-mentioned cycloalkyl groups and the cycloalkyl groups present within the other groups named may contain 5 to 10 carbon atoms, unless otherwise specified, and
the term xe2x80x9caroyl groupxe2x80x9d used above denotes, for example, the benzoyl or naphthoyl group.
The protecting groups mentioned in the foregoing definitions and hereinafter are the protecting groups which are commonly known from peptide chemistry, particularly
a phenylalkoxycarbonyl group having 1 to 3 carbon atoms in the alkoxy moiety, optionally substituted in the phenyl nucleus by a halogen atom, by a nitro or phenyl group or by one or two methoxy groups,
for example the benzyloxycarbonyl, 2-nitro-benzyloxycarbonyl, 4-nitro-benzyloxycarbonyl, 4-methoxy-benzyloxycarbonyl, 2-chloro-benzyloxycarbonyl, 3-chloro-benzyloxycarbonyl, 4-chloro-benzyloxycarbonyl, 4-Biphenylyl-xcex1,xcex1-dimethyl-benzyloxycarbonyl or 3,5-dimethoxy-xcex1,xcex1-dimethyl-benzyloxycarbonyl group,
an alkoxycarbonyl group having a total of 1 to 5 carbon atoms in the alkyl moiety,
for example the methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, 1-methylpropoxycarbonyl, 2-methylpropoxycarbonyl or tert.butyloxycarbonyl group,
the allyloxycarbonyl, 2,2,2-trichloro-(1,1-dimethylethoxy)carbonyl or 9-fluorenylmethoxycarbonyl group or
the formyl, acetyl or trifluoroacetyl group.
The present invention relates to racemates, where the compounds of general formula I have only one chiral element. However, the application also covers the individual diastereomeric pairs of antipodes or mixtures thereof which occur when there is more than one chiral element in the compounds of general formula (I).
Particularly preferred are compounds of general formula I wherein Z denotes NR1 and m assumes the value 0 and which are in the D- or (R)-configuration with regard to the partial amino acid structure of the formula 
and which are in the L- or (S)-configuration with regard to the partial amino acid structure of formula 
which may be present in the group A. As for the other compounds covered by general formula I, the preferred isomers are those which are spatially constructed analogously to the (R)-configured partial structure of formula V with regard to the partial structure of formula VI 
The compounds of general formula I have valuable pharmacological properties based on their selective CGRP-antagonistic properties. The invention further relates to medicaments containing these compounds, their use and the preparation thereof.
A subgroup of compounds of general formula I which deserves special mention comprises those wherein
A, R2, R3, R4, R11, X, Z and m and n are as hereinbefore defined and
R denotes an unbranched C1-6-alkylamino group optionally substituted at the nitrogen atom by a C1-6-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl- or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl-group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkylamino groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 4 carbon atoms, unless otherwise stated,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and the salts thereof.
Another subgroup of compounds of general formula I deserving special mention comprises those wherein
R2, R3, R4, R11, X, Z and m and n are defined as for the first subgroup hereinbefore,
R denotes an unbranched C1-7-alkyl group which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl- or biphenylyl-group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-2H-2-oxoimidazopyridinyl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl- or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl-groups, whilst the latter two groups may each be mono- or disubstituted in the 4- and/or 5-position or in the 5- and/or 6-position by lower straight-chained or branched alkyl groups, by phenyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl-1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl groups, and the substituents may be identical or different,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or in addition to a nitrogen atom contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom, which contains one, two or three nitrogen atoms,
whilst a 1,4-butadienylene group may be attached both to the above-mentioned 5-membered and to the 6-membered heteroaromatic monocyclic rings, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl- and biphenylyl-groups mentioned hereinbefore for the substitution of the alkyl groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C38-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group, and
A denotes a single bond,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 4 carbon atoms unless otherwise stated,
their tautomers, their diastereomers, their enantiomers and the salts thereof.
Preferred compounds of the above general formula I are those wherein
R denotes an unbranched C1-5-alkyl group which may be substituted in the xcfx89-position
by a C4-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-2H-2-oxoimidazopyridinyl, 1,3-dihydro-2(2H)-oxoimidazo[4,5c]quinolin-3-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl group, whilst the latter two groups may each be mono- or disubstituted in the 4- and/or 5-position or in the 5- and/or 6-positions by lower straight-chained or branched alkyl groups, by phenyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl-1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl groups, and the substituents may be identical or different,
by a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, an oxygen, sulphur or additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom and containing one or two nitrogen atoms,
whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
or an unbranched C1-4-alkylamino group optionally substituted at the nitrogen atom by a C1-3-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-7-cycloalkyl group, by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl or 1,3-dihydro-2H-2-oxo-imidazo[4,5-b]pyridin-3-yl group,
by a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, an oxygen, sulphur or additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1 or 2 nitrogen atoms, whilst a 1,4-butadienylene group may be attached to both the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl and alkylamino groups in the xcfx89-position and optionally also partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms or by alkyl groups, C5-7-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, wherein the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group, or the group of formula 
xe2x80x83wherein
p denotes the number 1 or 2,
o denotes the number 2 or, if Y1 and Y2 are not simultaneously nitrogen atoms, o may also denote 1.
Y1 denotes the nitrogen atom if R5 is a free pair of electrons, or the carbon atom,
Y2 is the nitrogen atom or the group  greater than CHxe2x80x94,
R5 is a free pair of electrons if Y1 denotes the nitrogen atom or, if Y1 denotes the carbon atom, R5 denotes a hydrogen atom, a C1-3-alkyl group, a hydroxy, cyano, aminocarbonyl, carboxy, alkoxycarbonyl, aminocarbonylamino, phenylmethyl or phenyl group,
R6 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom, R6 together with R5 may denote an additional bond,
R7 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom and R5 and R6 together constitute an additional bond, R7 together with RN may also denote a 1,4-butadienylene group,
RN denotes the hydrogen atom or a C1-3-alkyl group, which may be monosubstituted in the xcfx89-position
by a C5-7-cycloalkyl group or by a 1-naphthyl, 2-naphthyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, piperidinyl, morpholinyl, pyrrolidinyl, hexahydro-1H-1-azepinyl, aminocarbonyl, alkylaminocarbonyl, acetylamino, cyano, aminocarbonylamino or alkylaminocarbonylamino group, or may be mono- or disubstituted by phenyl, pyridinyl or diazinyl groups, whilst these substituents may be identical or different,
a cyclohexyl, phenyl, pyridinyl, cyano, amino, benzoylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonyl, phenylalkoxycarbonyl, aminocarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, N-(aminocarbonyl)-N-alkylamino, N-(alkylaminocarbonyl)-N-alkylamino, N-(alkylaminocarbonyl)-N-phenylamino, phenylaminocarbonylamino, [N-phenyl(alkylamino)]carbonylamino, N-(phenylaminocarbonyl)-N-alkylamino, N-(phenylaminocarbonyl)-N-phenylamino, benzoylaminocarbonylamino, phenylalkylaminocarbonylamino, pyridinylaminocarbonylamino, N-(aminocarbonyl)-N-phenylamino, N-(alkylaminocarbonyl)-N-phenylamino, N-(aminocarbonylaminocarbonyl)-N-phenylamino, N-(pyridinyl)-N-(aminocarbonyl)amino, N-(pyridinyl)-N-(alkylaminocarbonyl)amino, phenylamino, pyridinylamino, diazinylamino or 4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl group,
a saturated, mono- or diunsaturated 5- to 7-membered aza, diaza, triaza, oxaza, thiaza, thiadiaza- or S,S-dioxidothiadiaza heterocycle,
whilst the above-mentioned heterocycles may be linked via a carbon or nitrogen atom and
may contain one or two carbonyl groups adjacent to a nitrogen atom,
may be substituted at one of the nitrogen atoms by an alkyl, alkanoyl, aroyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, phenylalkoxycarbonylalkyl, phenylmethyl or phenyl group,
may be substituted at one or two carbon atoms by a branched or unbranched alkyl group, by a phenyl, phenylmethyl, naphthyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl group, whilst the substituents may be identical or different,
and wherein a C3-4-alkylene group may additionally be attached to the above-mentioned heterocycles via two adjacent carbon atoms or an olefinic double bond of one of the above-mentioned unsaturated heterocycles may be fused with a benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methyl-pyrrole, quinoline, imidazole or N-methylimidazole ring,
or, provided that Y1 is not a nitrogen atom and R5 and R6 together denote an additional bond, RN together with R7 may also denote the 1,4-butadienylene group or,
if Y1 denotes a carbon atom, RN together with R5 , with the inclusion of Y1, may also denote a carbonyl group or a saturated or monounsaturated 5- or 6-membered 1,3-diazaheterocycle which may contain one or two carbonyl groups in the ring adjacent to a nitrogen atom and, if it is unsaturated, may also be benzo-fused at the double bond and substituted at one of the nitrogen atoms by a methyl, aminocarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, phenylalkoxycarbonylalkyl, phenylmethyl or phenyl group,
whilst the phenyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl groups contained in the residues mentioned under R5, R7 and RN, as well as benzo-, thieno-, pyrido- and diazinofused heterocycles in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C4-7-cycloalkyl groups, nitro, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulphonylamino, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxyalkylaminocarbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino, aminocarbonylaminoalkyl, alkylaminocarbonylamino, alkanoyl, cyano, trifluoromethoxy, trifluormethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, wherein the substituents may be identical or different and the alkyl groups contained in the above-mentioned groups may contain 1 to 3 carbon atoms unless otherwise specified,
X denotes the oxygen atom or 2 hydrogen atoms,
Z denotes the methylene group or the group xe2x80x94NR5xe2x80x94 wherein
R1 denotes a hydrogen atom or a C1-3-alkyl group,
R11 denotes a hydrogen atom, a C1-3-alkyl group or an alkoxycarbonyl group having 2 to 4 carbon atoms altogether,
n denotes the number 1 or 2 or, if m is 1, n may also be 0,
m denotes the number 0 or 1,
R2 denotes a phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydro-1-naphthyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yl, 1-(1,1-dimethylethoxycarbonyl)-1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 2-thienyl, 3-thienyl, thiazolyl, 1H-indazol-3-yl, 1-methyl-1H-indazol-3-yl, benzo[b]fur-3-yl, benzo[b]thien-3-yl, pyridinyl, quinolinyl or isoquinolinyl group,
whilst the above-mentioned aromatic and heteroaromatic groups in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, or by branched or unbranched alkyl groups, C4-7-cycloalkyl groups, phenylalkyl groups, alkenyl, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonylalkyl, carboxyalkyl, alkoxycarbonyl, carboxy, dialkylaminoalkyl, dialkylaminoalkoxy, hydroxy, nitro, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, methylsulphonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, tetrazolyl, phenyl, pyridinyl, thiazolyl, furyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, and the substituents may be identical or different,
A denotes a bond or the divalent group of formula 
(linked to the R3R4Nxe2x80x94 group of general formula (I) via the carbonyl group)
xe2x80x83wherein
R8 and R9 together denote an n-propylene group or
R8 denotes a hydrogen atom or a C1-3-alkyl group and
R9 denotes a hydrogen atom or a branched or unbranched C1-4-alkyl group which, if it is unbranched, may be substituted in the xcfx89-position
by a hydroxy, mercapto, amino, alkylamino, dialkylamino, 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, hexahydro-1-azepinyl, methylthio, hydroxycarbonyl, aminocarbonyl, aminoiminomethylamino, aminocarbonylamino, phenyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 1-naphthyl, 2-naphthyl- or pyridinyl group, whilst the above-mentioned heterocycles and phenyl groups may in turn be mono-, di- or trisubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms, or by methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, trifluoromethoxy, methylsulphonyloxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and any hydroxy, mercapto, amino, guanidino, indolyl and imidazolyl groups contained in the groups mentioned for R9 may be substituted by a protecting group,
R3 denotes a hydrogen atom,
a C1-4-alkyl group which may be substituted in the xcfx89-position by a cyclohexyl, phenyl, pyridinyl, diazinyl, hydroxy, amino, alkylamino, dialkylamino, carboxy, aminocarbonyl, aminocarbonylamino, acetylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-(1-piperidinyl)-1-piperidinyl, 4-morpholinyl, hexahydro-1H-azepin-1-yl, [bis-(2-hydroxyethyl)]amino, 4-methyl-1-piperazinyl- or 4-(xcfx89-hydroxyalkyl)-1-piperazinyl group,
a phenyl or pyridinyl group,
wherein the above-mentioned heterocyclic radicals and phenyl groups may additionally be mono-, di- or tri-substituted in the carbon skeleton by fluorine, chlorine or bromine atoms or by methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, methylsulphonyloxy, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups and the substituents may be identical or different,
R4 denotes a hydrogen atom or a methyl or ethyl group optionally substituted by a phenyl or pyridinyl group
or R3 and R4 together with the enclosed nitrogen atom denote a group of general formula 
xe2x80x83wherein
Y3 denotes a carbon atom or, if R12 denotes a free pair of electrons, Y3 may also be the nitrogen atom,
r denotes the number 0, 1 or 2,
q denotes the number 0, 1 or 2,
R10 denotes a hydrogen atom or an amino, alkylamino, dialkylamino, alkyl, cycloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminoiminomethyl, aminocarbonylamino, alkylaminocarbonylamino, cycloalkylaminocarbonylamino, phenylaminocarbonylamino, aminocarbonylalkyl, aminocarbonylaminoalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxyalkyl or carboxy group,
a phenyl, pyridinyl, diazinyl, 1-naphthyl, 2-naphthyl, pyridinylcarbonyl or phenylcarbonyl group which may be mono-, di- or trisubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms, or by alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylaminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, xcfx89-(dialkylamino)alkanoyl, xcfx89-(dialkylamino)alkyl, xcfx89-(dialkylamino)hydroxyalkyl, xcfx89-(carboxy)alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl-oder trifluoromethylsulphonyl groups, whilst the substituents may be identical or different,
a 1,3-dihydro-2-oxo-2H-imidazolyl, 2,4(1H,3H)-dioxopyrimidinyl or 3,4-dihydro-2(1H)-oxopyrimidinyl group bound via a nitrogen atom, which may be substituted by a phenyl group or fused at the double bond to a benzene, pyridine or diazine ring,
a 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl group,
a 4- to 10-membered azacycloalkyl group, a 5- to 10-membered oxaza, thiaza or diazacycloalkyl group or a 6- to 10-membered azabicycloalkyl group,
wherein the above-mentioned mono- and bicyclic heterocycles may be bound via a nitrogen or carbon atom and
may be substituted by a C1-7-alkyl group, by an alkanoyl, dialkylamino, phenylcarbonyl, pyridinylcarbonyl, carboxyalkanoyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylsulphonyl, cycloalkyl or cycloalkylalkyl group, by a cycloalkylcarbonyl, azacycloalkylcarbonyl, diazacycloalkylcarbonyl or oxazacycloalkylcarbonyl group optionally alkyl substituted in the ring,
whilst the alicyclic parts contained in these substituents may comprise 3 to 10 ring members and the heteroalicyclic parts may comprise 4 to 10 ring members and
the above-mentioned phenyl and pyridinyl groups may in turn be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylaminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, xcfx89-(dialkylamino)alkanoyl, xcfx89-(carboxy)alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different, or
R10 together with R12 and Y3 denotes a 4- to 7-membered cycloaliphatic ring in which a methylene group may be replaced by an xe2x80x94NHxe2x80x94 or xe2x80x94N(alkyl)-group,
whilst a hydrogen atom bound to a nitrogen atom within the group R10 may be replaced by a protecting group,
R12 denotes a hydrogen atom, a C1-2-alkyl group which may be substituted in the xcfx89-position by a phenyl, pyridinyl, diazinyl, amino, alkylamino, dialkylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-methyl-1-piperazinyl, 4-morpholinyl or hexahydro-1H-azepin-1-yl-group,
an alkoxycarbonyl, cyano- or aminocarbonyl group or a free pair of electrons, if Y3 denotes a nitrogen atom, and
R13 and R14 in each case denote a hydrogen atom or,
if Y3 is a carbon atom, R12 together with R14 also denotes another carbon-carbon bond, wherein R10 is as hereinbefore defined and R13 denotes a hydrogen atom or
if Y1 is a carbon atom, R12 together with R14 also denotes another carbon-carbon bond and R10 together with R13 and the enclosed double bond denotes a partially hydrogenated or aromatic 5- to 7-membered mono- or bicyclic carbocycle or heterocycle,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 4 carbon atoms, unless otherwise specified,
all the above-mentioned cycloalkyl groups and the cycloalkyl groups present within the other groups named may contain 5 to 7 carbon atoms, unless otherwise specified, and
the term xe2x80x9caroyl groupxe2x80x9d used above denotes, for example, the benzoyl or naphthoyl group,
their tautomers, their diastereomers, their enantiomers and their salts.
One subgroup of preferred compounds of general formula I deserving special mention comprises those wherein
A, R2, R3, R4, R11, X, Z and m and n are defined as given hereinbefore defined for the preferred compounds of general formula I,
R denotes an unbranched C1-4-alkylamino group optionally substituted at the nitrogen atom by a C1-3-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl or 1,3-dihydro-2H-2-oxo-imidazo[4,5-b]pyridin-3-yl group,
by a 5-membered heteroaromatic ring linked via a carbon atom, and containing a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, an oxygen, sulphur or additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1 or 2 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkylamino groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C5-7-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 4 carbon atoms, unless otherwise stated,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and the salts thereof.
Another subgroup of compounds of general formula I deserving special mention comprises those wherein
R2, R3, R4, R11, X, Z and m and n are defined as for the first preferred subgroup hereinbefore,
R denotes an unbranched C1-5-alkyl group which may be substituted in the xcfx89-position
by a C4-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-2H-2-oxoimidazopyridinyl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl group, whilst the latter two groups may each be mono- or disubstituted in the 4- and/or 5-position or in the 5- and/or 6-position by lower straight-chained or branched alkyl groups, by phenyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl-1-methylpyrazolyl, imidazolyl or 1-methylimidazolyl groups, and the substituents may be identical or different,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or in addition to a nitrogen atom contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom, which contains one or two nitrogen atoms,
whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned hereinbefore for the substitution of the alkyl groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C5-7-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group, and
A denotes a single bond,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 4 carbon atoms unless otherwise stated,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and the salts thereof.
Preferred compounds of the above general formula I are those wherein
R denotes an unbranched C1-3-alkyl group which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl group, whilst the latter two groups may be substituted in the carbon skeleton by a phenyl, pyridinyl or diazinyl group,
by a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or two nitrogen atoms, wherein a nitrogen of an imino group may be substituted by an alkyl group,
or may be substituted by a pyridinyl group,
whilst a 1,4-butadienylene group may be attached both to the 5-membered heteroaromatic monocyclic rings and to the pyridinyl group, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
or an unbranched C1-4-alkylamino group optionally substituted at the nitrogen atom by a methyl or ethyl group, which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2(1H)-oxoquinolin-3-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl group,
by a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or two nitrogen atoms, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a pyridinyl group,
whilst a 1,4-butadienylene group may be attached both to the 5-membered heteroaromatic monocyclic rings and to the pyridinyl group, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned hereinbefore for the substitution of the alkyl and alkylamino groups in the xcfx89-position as well as optionally partially hydrogenated mono- and bicyclic heteroaromatic rings may additionally be mono- or disubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms or by alkyl, nitro, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, propionylamino, alkanoyl, cyano or trifluoromethoxy groups, whilst the substituents may be the same or different,
or the group of formula 
xe2x80x83wherein
p denotes the number 1 or 2,
o denotes the number 2 or, if Y1 and Y2 are not simultaneously nitrogen atoms, it may also denote the number 1,
Y1 denotes the nitrogen atom if R5 denotes a free pair of electrons, or the carbon atom,
Y2 denotes the nitrogen atom or the group  greater than CHxe2x80x94,
R5 denotes a free pair of electrons if Y1 denotes the nitrogen atom or, if Y1 denotes the carbon atom, R5 denotes a hydrogen atom, a C1-3-alkyl group, a hydroxy, cyano, aminocarbonyl, carboxy, alkoxycarbonyl or aminocarbonylamino group or a phenylmethyl or phenyl group optionally substituted at the aromatic moiety by a fluorine, chlorine or bromine atom or by a methyl, methoxy, ethoxy, trifluoromethyl, hydroxy, amino or acetylamino group,
R6 denotes the hydrogen atom or, if Y1 is not a nitrogen atom, R6 together with R5 may also denote an additional bond,
R7 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom and R5 and R6 together denote an additional bond, R7 together with RN may also denote the 1,4-butadienylene group,
RN denotes the hydrogen atom or a C1-3-alkyl group, which may be monosubstituted in the xcfx89-position
by a C5-7-cycloalkyl group or by a 1-naphthyl, 2-naphthyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, piperidinyl, morpholinyl, pyrrolidinyl, hexahydro-1H-1-azepinyl, aminocarbonyl, methylaminocarbonyl, acetylamino, cyano, aminocarbonylamino or alkylaminocarbonylamino group, or may be mono- or disubstituted by phenyl, pyridinyl or diazinyl groups, whilst these substituents may be identical or different,
a cyclohexyl, phenyl, pyridinyl, cyano, amino, benzoylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonyl, phenylalkoxycarbonyl, aminocarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, N-(aminocarbonyl)-N-alkylamino, N-(alkylaminocarbonyl)-N-alkylamino, N-(alkylaminocarbonyl)-N-phenylamino, phenylaminocarbonylamino, [N-phenyl(alkylamino)]carbonylamino, N-(phenylaminocarbonyl)-N-alkylamino, N-(phenylaminocarbonyl)-N-phenylamino, benzoylaminocarbonylamino, phenylalkylaminocarbonylamino, pyridinylaminocarbonylamino, N-(aminocarbonyl)-N-phenylamino, N-(alkylaminocarbonyl)-N-phenylamino, N-(aminocarbonylaminocarbonyl)-N-phenylamino, N-(pyridinyl)-N-(aminocarbonyl)amino, N-(pyridinyl)-N-(alkylaminocarbonyl)amino, phenylamino, pyridinylamino, diazinylamino or 4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl group,
a saturated, mono- or diunsaturated 5- to 7-membered aza, diaza, triaza, oxaza, thiaza, thiadiaza or S,S-dioxidothiadiaza heterocycle,
whilst the above-mentioned heterocycles may be linked via a carbon or nitrogen atom and
may contain one or two carbonyl groups adjacent to a nitrogen atom,
may be substituted at one of the nitrogen atoms by an alkyl, alkanoyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, phenylalkoxycarbonylalkyl, phenylmethyl or phenyl group,
may be substituted at one or two carbon atoms by a methyl, phenyl, phenylmethyl, naphthyl, biphenylyl, thienyl, pyridinyl or diazinyl group, wherein the substituents may be identical or different,
and wherein a C3-4-alkylene group may additionally be attached to the above-mentioned heterocycles via two adjacent carbon atoms or an olefinic double bond of one of the above-mentioned heterocycles may be fused to a thiophene, benzene, pyridine, quinoline or diazine ring,
or, if Y1 is not a nitrogen atom and R5 and R6 together denote an additional bond, RN together with R7 may also denote a 1,4-butadienylene group or,
if Y1 denotes a carbon atom, RN together with R5 with the inclusion of Y1 may also denote a carbonyl group or a saturated or monounsaturated 5- or 6-membered 1,3-diazaheterocycle which may contain one or two carbonyl groups in the ring adjacent to a nitrogen atom and, if it is unsaturated, may also be benzo-fused at the double bond and may be substituted at one of the nitrogen atoms by a methyl, aminocarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, phenylalkoxycarbonylalkyl, phenylmethyl or phenyl group,
whilst the phenyl, pyridinyl or diazinyl groups contained in the groups mentioned under RN and the thieno-, benzo-, pyrido- or diazino-condensed heterocycles in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by methyl groups, nitro, methoxy, ethoxy, methylsulphonylamino, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, hydroxy, amino, acetylamino, propionylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, hydroxyalkylaminocarbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino, aminocarbonylaminoalkyl, methylaminocarbonylamino, acetyl, cyano or trifluoromethoxy groups, whilst the substituents may be identical or different,
and the alkyl groups contained in the above-mentioned radicals may contain 1 to 3 carbon atoms, unless otherwise specified,
X denotes an oxygen atom or 2 hydrogen atoms,
Z denotes a methylene group or the group xe2x80x94NR1xe2x80x94 wherein
R1 is a hydrogen atom or a methyl group,
R11 denotes the hydrogen atom or a methyl or methoxycarbonyl group,
n denotes the number 1 or 2 or, if m is the number 1, n may also denote 0,
m denotes the number 0 or 1,
R2 denotes a phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydro-1-naphthyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yl, 1-(1,1-dimethylethoxycarbonyl)-1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 2-thienyl, 3-thienyl, thiazolyl, pyridinyl or quinolinyl group,
wherein the above-mentioned aromatic and heteroaromatic groups may additionally be mono-, di- or trisubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms, by branched or unbranched C1-5-alkyl groups, allyl, vinyl, methoxy, ethoxy, propoxy, 1-methylethoxy, dimethylaminoethoxy, trifluoromethyl, hydroxy, nitro, amino, acetylamino, propionylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, acetyl, cyano, methylsulphonyloxy or trifluoromethoxy groups, by tetrazolyl, phenyl pyridinyl, thiazolyl or furyl groups and the substituents may be identical or different, or
A denotes a bond or the divalent group of formula 
(linked to the NR3R4-group of general formula (I) via the carbonyl group)
xe2x80x83wherein
R8 and R9 together denote an n-propylene group or
R8 denotes the hydrogen atom or the methyl group and
R9 denotes a hydrogen atom or an unbranched C1-4-alkyl group which may be substituted in the xcfx89-position
by a hydroxy, amino, methylamino, dimethylamino, hydroxycarbonyl, aminocarbonyl, aminoiminomethylamino, aminocarbonylamino, phenyl or pyridinyl group, wherein the phenyl and pyridinyl group may in turn be substituted in the carbon skeleton by a fluorine, chlorine or bromine atom or by a methyl, methoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl or cyano group and wherein any hydroxy, amino and guanidino groups contained in the groups given for R9 may be substituted by a protecting group, e.g. the phenylmethoxycarbonyl or tert.butyloxycarbonyl group,
R3 denotes a hydrogen atom,
a C1-4-alkyl group optionally substituted in the xcfx89-position by a cyclohexyl, phenyl, pyridinyl, hydroxy, amino, methylamino, dimethylamino, carboxy, aminocarbonyl, aminocarbonylamino, acetylamino, 1-pyrrolidinyl, 1-piperidinyl or 4-(1-piperidinyl)-1-piperidinyl group,
a phenyl or pyridinyl group,
whilst the above-mentioned phenyl and pyridinyl groups may additionally be substituted in the carbon skeleton by a fluorine, chlorine or bromine atom or by a methyl, methoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl or cyano group,
R4 denotes the hydrogen atom or a C1-2-alkyl group optionally substituted by a phenyl or pyridinyl group
or R3 and R4 together with the enclosed nitrogen atom denote a group of general formula 
xe2x80x83wherein
Y3 denotes a carbon atom or, if R12 denotes a free pair of electrons, Y3 may also be a nitrogen atom,
r denotes the number 0, 1 or 2,
q denotes the number 0, 1 or 2,
with the proviso that the sum of the numbers given for r and q is 0, 1, 2 or 3,
R10 denotes a hydrogen atom, an alkyl, cycloalkyl, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonylamino, alkoxycarbonyl, alkoxycarbonylmethyl, carboxymethyl or carboxy group,
a phenyl, pyridinyl, diazinyl, pyridinylcarbonyl or phenylcarbonyl group which may be mono- or disubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms, or by methyl, ethyl, propyl, methoxy, hydroxy, xcfx89-(dialkylamino)-alkyl, xcfx89-(dialkylamino)hydroxyalkyl or alkanoyl groups, whilst the substituents may be identical or different,
a 1,3-dihydro-2-oxo-2H-imidazolyl, 2,4(1H,3H)-dioxopyrimidinyl or 3,4-dihydro-2(1H)-oxopyrimidinyl group bound via a nitrogen atom, which may be substituted by a phenyl group or may be fused at the double bond to a benzene, pyridine or diazine ring,
a 5- to 7-membered azacycloalkyl group, a 4- to 7-membered oxaza- or diazacycloalkyl group or a 7- to 9-membered azabicycloalkyl group,
wherein the above-mentioned mono- and bicyclic heterocycles are bound via a nitrogen or a carbon atom and
may be substituted by a C1-7-alkyl group, or by an alkanoyl, dialkylamino, phenylcarbonyl, carboxyalkanoyl, carboxyalkyl, alkoxycarbonylalkyl or alkoxycarbonyl group having 1 to 4 carbon atoms in the alkoxy moiety, alkylsulphonyl, cycloalkyl or cycloalkylalkyl group or by an azacycloalkylcarbonyl or diazacycloalkylcarbonyl group optionally alkylsubstituted in the ring,
whilst the alicyclic groups contained in these substituents may comprise 3 to 7 ring members and the heteroalicyclic groups may comprise 4 to 7 ring members and
the above-mentioned phenylcarbonyl group may be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy, trifluoromethyl, hydroxy, amino or acetylamino group, or
R10 together with R12 and Y3 denotes a 4- to 6-membered cycloaliphatic ring in which a methylene group may be replaced by an xe2x80x94NHxe2x80x94 or xe2x80x94N(CH3)-group,
whilst a hydrogen atom bound to a nitrogen atom within the group R10 may be replaced by a protecting group, e.g. the phenylmethoxycarbonyl or tert.butyloxycarbonyl group,
R12 denotes a hydrogen atom, a C1-2-alkyl group which may be substituted in the xcfx89-position by a phenyl, pyridinyl, amino, alkylamino, dialkylamino, 1-pyrrolidinyl, 1-piperidinyl or 4-methyl-1-piperazinyl group,
a methoxycarbonyl or ethoxycarbonyl, cyano or aminocarbonyl group or a free pair of electrons, if Y3 denotes a nitrogen atom, and
R13 and R14 each denote a hydrogen atom or,
if Y3 is a carbon atom, R12 together with R14 also denotes another carbon-carbon bond, wherein R10 is as hereinbefore defined and R13 denotes a hydrogen atom, or
if Y3 is a carbon atom, R12 together with R14 also denotes another carbon-carbon bond and R10 together with R13 and the enclosed double bond denotes a partially hydrogenated or aromatic 5- or 6-membered mono- or bicyclic carbocycle or heterocycle, containing one or two nitrogen atoms,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups named may contain 1 to 3 carbon atoms, unless otherwise stated, and
all the above-mentioned cycloalkyl groups and the cycloalkyl groups present within the other groups named may contain 5 to 7 carbon atoms, unless otherwise specified,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and the salts thereof.
One subgroup of particularly preferred compounds of general formula I deserving special mention comprises those wherein
A, R2, R3, R4, R11, X, Z and m and n are defined as for the particularly preferred compounds of general formula I hereinbefore and
R denotes an unbranched C1-4-alkylamino group optionally substituted at the nitrogen atom by a methyl or ethyl group, which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2(1H)-oxoquinolin-3-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl group,
by a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or two nitrogen atoms, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a pyridinyl group,
whilst a 1,4-butadienylene group may be attached both to the 5-membered heteroaromatic monocyclic rings and also to the pyridinyl group, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned hereinbefore for the substitution of the alkylamino groups in the xcfx89-position, as well as optionally any partially hydrogenated mono- and bicyclic heteroaromatic rings, may additionally be mono- or disubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms or by alkyl, nitro, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, propionylamino, alkanoyl, cyano or trifluoromethoxy groups, whilst the substituents may be identical or different,
whilst all the above-mentioned alkyl and alkoxy groups and the alkoxy groups present within the other named radicals may contain 1 to 3 carbon atoms unless otherwise stated,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and the salts thereof.
Another subgroup of particularly preferred compounds of general formula I which deserves special mention comprises those compounds wherein
R2, R3, R4, R11, X, Z and m and n are as hereinbefore defined for the first-mentioned particularly preferred subgroup,
R denotes an unbranched C1-3-alkyl group which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl group, whilst the latter two groups may be substituted in the carbon skeleton by a phenyl, pyridinyl or diazinyl group,
by a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or two nitrogen atoms, wherein a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a pyridinyl group,
whilst a 1,4-butadienylene group may be attached both to the 5-membered heteroaromatic monocyclic rings and also to the pyridinyl group via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned hereinbefore for the substitution of the alkyl groups in the xcfx89-position as well as optionally any partially hydrogenated mono- and bicyclic heteroaromatic rings may additionally be mono- or disubstituted in the carbon skeleton by fluorine, chlorine or bromine atoms or by alkyl, nitro, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, propionylamino, alkanoyl, cyano or trifluoromethoxy groups wherein the substituents may be identical or different,
and A denotes a single bond,
whilst all the above-mentioned alkyl and alkoxy groups and the alkyl groups present within the other groups mentioned may contain 1 to 3 carbon atoms unless otherwise specified,
their tautomers, their diastereomers, their enantiomers and their salts.
More particularly preferred compounds of the above general formula I are those wherein
R denotes an unbranched C1-3-alkyl group which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group, whilst the above-mentioned aromatic groups may additionally be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy, amino or acetylamino group,
by a 2-pyrrolyl, 3-pyrrolyl, pyridinyl, 1H-indol-3-yl, quinolinyl or isoquinolinyl group,
or an unbranched C1-4-alkylamino group which is optionally additionally substituted at the nitrogen atom by a methyl or ethyl group and which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by a phenyl group which may be mono- or disubstituted by fluorine, chlorine or bromine atoms, or by methyl, nitro, methoxy, trifluoromethyl, hydroxy, amino or acetylamino groups, whilst the substituents may be identical or different,
by a 2-pyrrolyl, 3-pyrrolyl, pyridinyl, 1H-indol-3-yl, quinolinyl or isoquinolinyl group,
or the group of formula 
xe2x80x83wherein
p denotes the number 1 or 2,
o denotes the number 2 or, if Y1 and Y2 are not simultaneously nitrogen atoms, it may also denote the number 1,
Y1 denotes the nitrogen atom if R5 denotes a free pair of electrons, or the carbon atom,
Y2 denotes the nitrogen atom or the group  greater than CHxe2x80x94,
R5 denotes a free pair of electrons, if Y1 denotes the nitrogen atom or, if Y1 denotes the carbon atom, R5 may denote the hydrogen atom, a C1-2-alkyl group or the cyano or phenyl group,
R6 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom, R6 together with R5 may also denote an additional bond,
R7 denotes the hydrogen atom or, provided that Y1 is not a nitrogen atom and R5 and R6 together denote an additional bond, R7 together with RN may also denote the 1,4-butadienylene group,
RN denotes the hydrogen atom or a C1-3-alkyl group, which may be substituted in the xcfx89-position
by one or two phenyl or pyridinyl groups, wherein the substituents may be identical or different,
or by a hydroxy or methoxy group,
a phenyl group which may be mono- or disubstituted by fluorine, chlorine or bromine atoms or by methyl groups, nitro, methoxy, ethoxy, trifluoromethyl, hydroxy or cyano groups, whilst the substituents may be identical or different, or a phenyl group substituted by a methylenedioxy group,
a 2-pyridinyl or 4-pyridinyl group,
an amino, benzoylamino, aminocarbonyl, methylaminocarbonyl, methoxycarbonyl, ethoxycarbonyl, aminocarbonylamino, methylaminocarbonylamino, N-(aminocarbonyl)-N-methylamino, N-(methylaminocarbonyl)-N-methylamino, N-(aminocarbonyl)-N-(4-fluorophenyl)amino, N-(methylaminocarbonyl)-N-phenylamino, phenylaminocarbonylamino, [N-phenyl(methylamino)]carbonylamino, N-(phenylaminocarbonyl)-N-methylamino, N-(phenylaminocarbonyl)-N-phenylamino, benzoylaminocarbonylamino, N-(aminocarbonyl)-N-phenylamino group or a phenylamino group optionally substituted in the phenyl ring by an aminocarbonylamino or methylsulphonylamino group,
a 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, a 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxobenzimidazol-1-yl, 1,3,3a,4,5,6,7,7a-octahydro-2(2H)-oxobenzimidazol-1-yl, 1H-indol-3-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl, 1,3(2H)-dioxo-1H-isoindol-2-yl, 1H-benzimidazol-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 2(3H)-oxobenzoxazol-3-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-d]pyrimidin-3-yl, 2,3,4,5-tetrahydro-2(1H)-oxo-1,3-benzodiazepin-3-yl, 3,4-dihydro-2(1H)-oxopyrido[2,3-d]pyrimidin-3-yl, 2(1H)-oxoquinolin-3-yl, 3,4-dihydro-2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 3,4,4a,5,6,7,8,8a-octahydro-2(1H)-oxoquinazolin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl, 1,3-dihydro-5-methyl-4-phenyl-2(2H)-oxoimidazol-1-yl, 2,5-dioxo-4-phenylimidazolidin-1-yl, 2,5-dioxo-4-(phenylmethyl)-imidazolidin-1-yl, 3,4-dihydro-2,2-dioxido-2,1,3-benzothiadiazin-3-yl, 1,3-dihydro-4-(4-biphenylyl)-2(2H)-oxoimidazol-1-yl, 1,3-dihydro-4-(2-naphthyl)-2(2H)-oxoimidazol-1-yl, 1,3-dihydro-4,5-diphenyl-2(2H)-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 4-phenyl-2(1H)-oxopyrimidin-1-yl, 4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl, 3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2[1H]-oxopyrido[4,3-d]pyrimidin-3-yl or 2,3-dihydro-4(1H)-oxoquinazolin-3-yl group,
wherein the above-mentioned mono- and bicyclic heterocycles may be substituted at one of the nitrogen atoms by a methoxycarbonylmethyl group and/or
the above-mentioned mono- and bicyclic heterocycles may be mono-, di- or trisubstituted in the carbon skeleton and/or at the phenyl groups contained in these groups by fluorine, chlorine or bromine atoms, or by methyl, trifluoromethyl, methoxy, hydroxy, amino, nitro, phenyl, phenylmethyl, carboxy, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, methylaminocarbonyl, hydroxyethylaminocarbonyl, (4-morpholinyl)carbonyl, (1-piperidinyl)carbonyl or (4-methyl-1-piperazinyl)carbonyl groups wherein the substituents may be identical or different and multiple substitution with the last three substituents is ruled out,
or, provided that Y1 is not a nitrogen atom and R5 and R6 together denote an additional bond, RN together with R7 also denotes the 1,4-butadienylene group,
or, provided that Y1 denotes a carbon atom, RN together with R5 with the inclusion of Y1 may also denote a carbonyl group or saturated or monounsaturated five- or six-membered 1,3-diaza-heterocycle,
which may contain a carbonyl group in the ring, adjacent to a nitrogen atom,
may be substituted by a phenyl group at one of the nitrogen atoms
and, if it is unsaturated, may also be benzo-condensed at the double bond,
X denotes an oxygen atom or 2 hydrogen atoms,
Z denotes a methylene group or the group xe2x80x94NR1, wherein
R1 denotes a hydrogen atom or a methyl group,
R11 denotes a hydrogen atom, a methoxycarbonyl, ethoxycarbonyl or methyl group,
n denotes the number 1 and m denotes the number 0 or
n denotes the number 0 and m denotes the number 1,
R2 denotes a phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydro-1-naphthyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-(1,1-dimethylethoxycarbonyl)-1H-indol-3-yl, 2-thienyl, 3-thienyl, thiazolyl or alkylthiazolyl group having 1 to 3 carbon atoms in the alkyl moiety, a pyridinyl or quinolinyl group,
wherein the above-mentioned phenyl and naphthyl groups may be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms or by branched or unbranched C1-5-alkyl groups, by C1-3-alkoxy groups, by vinyl, allyl, trifluoromethyl, methylsulphonyloxy, 2-(dimethylamino)ethoxy, hydroxy, cyano, nitro or amino groups, by tetrazolyl, phenyl, pyridinyl, thiazolyl or furyl groups and the substituents may be identical or different, and multiple substitution with the last five substituents is ruled out,
A denotes a bond or the divalent group of formula 
(linked to the group xe2x80x94NR3R4 of formula (I) via the carbonyl group)
xe2x80x83wherein
R8 and R9 together denote an n-propylene group or
R8 denotes the hydrogen atom or the methyl group and
R9 denotes the hydrogen atom or an unbranched C1-4-alkyl group,
which may be substituted in the xcfx89-position by an amino, methylamino, dimethylamino, aminoiminomethylamino or aminocarbonylamino group, whilst in the above-mentioned substituents a hydrogen atom bound to a nitrogen atom may be replaced by a protecting group, e.g. the phenylmethoxycarbonyl or tert.butyloxycarbonyl group,
R3 denotes a hydrogen atom or
a C1-4-alkyl group optionally substituted in the xcfx89-position by an amino, methylamino, dimethylamino- or 4-(1-piperidinyl)-1-piperidinyl group,
R4 denotes a hydrogen atom or a methyl or ethyl group
or R3 and R4 together with the enclosed nitrogen atom denote a group of general formula 
xe2x80x83wherein
Y3 denotes the carbon atom or, if R12 denotes a free pair of electrons, Y3 may also denote a nitrogen atom,
r denotes the number 1,
q denotes the number 1,
R10 denotes the hydrogen atom, an alkyl, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonylamino, alkoxycarbonyl, alkoxycarbonylmethyl, carboxymethyl or carboxy group or a cycloalkyl group having 4 to 7 carbon atoms in the ring,
a benzoyl, pyridinylcarbonyl, phenyl, pyridinyl or diazinyl group, each of which may be substituted in the carbon skeleton by a fluorine, chlorine or bromine atom, or by an acetyl, methyl, ethyl or methoxy group, or by a dimethylaminoalkyl group having 1 to 4 carbon atoms in the alkyl moiety optionally hydroxysubstituted in the alkyl moiety,
a 1,3-dihydro-2-oxo-2H-imidazolyl group bound via a nitrogen atom, which may be fused to a benzene or pyridine ring at the double bond,
a 1-pyrrolidinyl, 1-piperidinyl, 4-(dimethylamino)-1-piperidinyl, 4-piperidinyl or 4-morpholinyl group, wherein the nitrogen atom of the 4-piperidinyl group may be substituted by an alkanoyl- or alkyl group each having 1 to 7 carbon atoms or by a benzoyl, methylsulphonyl, 3-carboxy-propionyl, cyclopropylmethyl, alkoxycarbonylmethyl or carboxymethyl group or by a protecting group, e.g. the phenylmethoxycarbonyl or tert.butyloxycarbonyl group, or it may represent a hexahydro-1H-1-azepinyl, 8-methyl-8-azabicyclo[3,2,1]oct-3-yl, 4-alkyl-1-piperazinyl, hexahydro-4-alkyl-1H-1,4-diazepin-1-yl, 1-alkyl-4-piperidinylcarbonyl or 4-alkyl-1-piperazinylcarbonyl group, or
R10 together with R12 and Y3 denotes a 5-membered cycloaliphatic ring in which a methylene group may be replaced by an xe2x80x94NHxe2x80x94 or xe2x80x94N(CH3)xe2x80x94 group,
R12 denotes a hydrogen atom, a C1-2-alkyl group which may be substituted in the xcfx89-position by a 1-pyrrolidinyl, 1-piperidinyl or 4-methyl-1-piperazinyl group,
a methoxycarbonyl or ethoxycarbonyl or a cyano group,
a free pair of electrons if Y3 denotes a nitrogen atom, and
R13 and R14 each denote a hydrogen atom or,
provided that Y3 is a carbon atom, R12 together with R14 may also denote an additional carbon-carbon bond, wherein R10 is as hereinbefore defined and R13 denotes a hydrogen atom or,
provided that Y3 is a carbon atom, R12 together with R14 may also denote an additional carbon-carbon bond and R10 together with R13 and the enclosed double bond denotes an indole group fused on via the 5-membered ring,
whilst all the above-mentioned alkyl groups and the alkyl groups present within the other named groups may contain 1 to 3 carbon atoms, unless otherwise specified,
their tautomers, their diastereomers, their enantiomers and their salts.
A subgroup of most particularly preferred compounds of general formula I deserving special mention comprises those wherein
A, R2, R3, R4, R11, X, Z and m and n are as hereinbefore defined for the most particularly preferred compounds of general formula I and
R denotes an unbranched C1-4-alkylamino group optionally substituted at the nitrogen atom by a methyl or ethyl group, which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by a phenyl group, which may be mono- or disubstituted by fluorine, chlorine or bromine atoms or by methyl, nitro, methoxy, trifluoromethyl, hydroxy, amino or acetylamino groups, wherein the substituents may be identical or different, or
by a 2-pyrrolyl, 3-pyrrolyl, pyridinyl, 1H-indol-3-yl, quinolinyl or isoquinolinyl group,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and salts thereof.
Another subgroup of most particularly preferred compounds of general formula I deserving special mention comprises those wherein
R2, R3, R4, R11, X, Z and m and n are as defined hereinbefore for the first-mentioned particularly preferred subgroup,
R denotes an unbranched C1-3-alkyl group which may be substituted in the xcfx89-position
by a C5-7-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or (4-biphenylyl) group, whilst the above-mentioned aromatic groups may be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy, amino or acetylamino group,
or by a 2-pyrrolyl, 3-pyrrolyl, pyridinyl, 1H-indol-3-yl, quinolinyl- or isoquinolinyl group,
and A denotes a single bond,
their tautomers, their diastereomers, their enantiomers, mixtures thereof and the salts thereof.
The following are mentioned as examples of most particularly preferred compounds:
(1) 1-[N2-[N-[[[2-(2-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(2) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(3) 1-[N2-[N-[[[2-(2,5-Dimethoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(4) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-arginyl]-4-(4-pyridinyl)-piperazine
(5) 1-[N2-[N-[[[2-(2,3-dimethoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(6) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D,L-tyrosyl]-D,L-lysyl]-4-(1-methyl-4-piperidinyl)-piperazine
(7) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D,L-tyrosyl]-D,L-lysyl]-4-(4-piperidinyl)-piperazine
(8) 1-[N2-[N-[[[2-(3,4-dihydroxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D,L-tyrosyl]-D,L-lysyl]-4-(4-pyridinyl)-piperazine
(9) 1-[N2-[N-[4-(2-Methoxyphenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(10) 1-[N2-[N-[4-(3-Methoxyphenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(11) 1-[N2-[N-[[(2-Phenylethyl)amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(12) 1-[N2-[N-[[[2-(4-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(13) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]amino]carbonyl]-3-(1-naphthyl)-D-alanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(14) 1-[N2-[N-[[[2-(3-Hydroxyphenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(15) 1-[N2-[N-[3-(3-Methoxyphenyl)-1-oxopropyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(16) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]methylamino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(17) 1-[N2-[N-(4-Phenyl-1-piperazinyl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(18) 1-[N2-[N-[4-(2-Methylphenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(19) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(20) 1-[N2-[N-[[[2-(3-Methoxyphenyl)ethyl]amino]carbonyl]-3,5-dichloro-D,L-tyrosyl]-D,L-lysyl]-4-(4-pyridinyl)-piperazine
(21) 1-[N2-[N-[4-(2-Methoxyphenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidin
(22) 1-[N2-[N-(4,4-Diphenyl-1-piperidinyl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(23) 1-[N2-[N-(4-Phenyl-1-piperidinyl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(24) 1-[N2-[N-[4-(4-Fluorophenyl)-1-oxobutyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(25) 1-[N2-[N-[4,4-Diphenyl-1-oxobutyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(26) 1-[N2-[N-[4-Cyclohexyl-1-oxobutyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(27) 1-[N2-[N-[4-(4-Acetylamino phenyl)-1-oxobutyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(28) 1-[N2-[N-[4-(2-Methoxyphenyl)-1-piperazinyl]carbonyl]-3,5-dichloro-D,L-tyrosyl]-D,L-lysyl]-4-(4-pyridinyl)-piperazine
(29) 1-[N2-[N-[4-[3-(Trifluoromethyl)phenyl]-1-piperazinyl]carbonyl]-3,5-dibromo-D,L-tyrosyl]-D,L-lysyl]-4-(4-pyridinyl)-piperazine
(30) 1-[N2-[N-[4-(2-Chlorophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(31) 1-[N2-[N-[4-(3,4-Methylenedioxy phenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(32) 1-[N2-[N-(4-Methyl-1-piperazinyl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(33) 1-[N2-[N-[4-(2-Hydroxyethyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(34) 1-[N2-[N-[4-(4-Pyridinyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(35) 1-[N2-[N-[4-(2-Pyridinyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(36) 1-[N2-[N-[4-(Diphenylmethyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(37) 1-[N2-[N-[4-(Phenylmethyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(38) 1-[N2-[N-[4-(4-Nitrophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(39) 1-[N2-[N-[4-(Ethoxycarbonyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(40) 1-[N2-[N-[[[3-(2-Methoxyphenyl)propyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(41) 1-[N2-[N-[[[2-(3-Bromophenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(42) 1-[N2-[N-[[[2-(3-Nitrophenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(43) 1-[N2-[N-[[[2-(3-Acetylaminophenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(44) 1-[N2-[N-[[[2-(3-Bromophenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(45) 1-[N2-[N-[(1,2,4,5-Tetrahydro-3H-3-benzazepin-3-yl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(46) 1-[N2-[N-[[[2-[3-(Trifluoromethyl)phenyl]ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(47) 1-[N2-[N-[[[2-(3-Fluorophenyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(48) 1-[N2-[N-[4-(2-Methoxyphenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-fluorophenyl)-piperazine
(49) 1-[N2-[4-Amino-3,5-dibromo-N-[[(2-phenylethyl)amino]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(50) 1-[N2-[N-[4-(2-Methoxyphenyl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(51) 1-[N2-[N-[4-(3-Methoxyphenyl)-1,2,5,6-tetrahydro-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(52) 1-[N2-[N-[4-(2-Methoxyphenyl)-1,2,5,6-tetrahydro-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(53) 1-[N2-[N-[(4-Biphenylyl)acetyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(54) 1-[N2-[N-[4-(4-Bromophenyl)-1-oxobutyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(55) 1-[N2-[N-[4-(1H-Indol-3-yl)-1-oxobutyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(56) 1-[N2-[N-(4,4-Diphenyl-1-piperidinyl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(57) 1-[N2-[N-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(58) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(59) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(60) 1-[N2-[N-[4-(2-Chlorophenyl)-1-piperazinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(61) 1-[N2-[N-[4-(2-Chlorophenyl)-1-piperazinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(62) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(2-pyridinyl)-piperazine
(63) 1-[N2-[N-[[[2-(2-Cyclohexyl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(64) 1-[N2-[N-[4-(2-Chlorophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(65) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(66) 1-[N2-[N-[4-(Aminocarbonyl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(67) 1-[N2-[N-[[[2-(1H-Indol-3-yl)ethyl]amino]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(68) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(2-methoxyphenyl)-piperazine
(69) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(2-pyridinyl)-piperazine
(70) 1-[N2-[N-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(2-methoxyphenyl)-piperazine
(71) 1-[N2-[N-(4,4-Diphenyl-1-piperidinyl)carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(2-pyridinyl)-piperazine
(72) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D,L-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(73) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D,L-phenylalanyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(74) 1-[N2-[N-[4-(2,3-Dichlorophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(75) 1-[N2-[N-[4-(3,5-Dichlorophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(76) 1-[N2-[N-[4-(2-Cyanphenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(77) 1-[N2-[N-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-3,5-dibromo-D,L-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(78) 1-[N2-[N-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-3,5-dibromo-D,L-phenylalanyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(79) 1-[N2-[N-[4-[4-Chloro-3-(trifluoromethyl)phenyl]-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(80) 1-[N2-[N-[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(81) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(82) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(83) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(84) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-[1-(1-methylethyl)-4-piperidinyl]-piperidine
(85) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-phenylpiperazine
(86) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-6-methyl-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(87) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-5-methyl-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(88) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-5,6-dichloro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(89) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-3-(methoxycarbonylmethyl)-2(2H)-oxobenzimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(90) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-piperidinyl)-piperidine
(91) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3,3a,4,5,6,7,7a-octahydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(92) 1-[4-Amino-3,5-dibromo-N-[[4-(benzoylamino))-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(93) 1-[4-Amino-3,5-dibromo-N-[[4-(aminocarbonyl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(94) 1-[4-Amino-3,5-dibromo-N-[(4-Oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(95) 1-[3,5-Dibromo-N-[[4-(benzoylamino)-1-piperidinyl]caronyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(96) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-6-methyl-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(97) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-5-methyl-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(98) 3,5-Dibromo-N2-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosinamide
(99) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-methylpiperazine
(100) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)piperazine
(101) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-phenylpiperazine
(102) 3,5-Dibromo-N2-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-N,N-diethyl-D-tyrosinamide
(103) 3,5-Dibromo-N2-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-N-[(4-(dimethylamino)butyl]-D-tyrosinamide
(104) 1-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(105) 1-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(106) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-(1,1-dimethylethoxycarbonyl)-4-piperidinyl]piperazine
(107) 1-[4-Amino-3,5-dibromo-N-[(4-cyan-4-phenyl-1-piperidinyl)carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(108) 1-[3,5-Dibromo-N-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(109) 1-[3,5-Dibromo-N-[(4-cyan-4-phenyl-1-piperidinyl)carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(110) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-pyridinyl)-piperazine
(111) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-pyrimidinyl)-piperazine
(112) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(2-pyridinyl)-piperazine
(113) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4(pyrazinyl)-piperazine
(114) 1-[4-Amino-3,5-dibromo-N-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-phenylalanyl]-4-(2-pyridinyl)-piperazine
(115) 1-[3,5-Dibromo-N-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-tyrosyl]-4-(2-pyridinyl)-piperazine
(116) 1-[4-Amino-3,5-dibromo-N-[[4-(2,4(1H,3H)-dioxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(117) 1-[3,5-Dibromo-N-[[4-(2,4(1H,3H)-dioxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(118) 1-[3,5-Dibromo-N-[[4-(aminocarbonyl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(119) 1-[4-Amino-3,5-dibromo-N-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-phenylalanyl]-4-(pyrazinyl)-piperazine
(120) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(2-pyrimidinyl)-piperazine
(121) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxo-imidazo[4,5-b]pyridin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(122) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(123) cis-1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-cyclohexyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(124) trans-1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-cyclohexyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(125) 1-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dimethyl-D,L-tyrosyl]-4-(4-pyridinyl)-piperazine
(126) 1-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dimethyl-D,L-tyrosyl]-4-(4-pyridinyl)-piperidine
(127) 1-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dimethyl-D,L-tyrosyl]-4-(1-piperidinyl)-piperidine
(128) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-fluorophenyl)-piperazine
(129) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(pyrazinyl)-piperazine
(130) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-methoxyphenyl)-piperazine
(131) 1-[4-Amino-3,5-dibromo-N-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-phenylalanyl]-4-(2-methoxyphenyl)-piperazine
(132) 1-[4-Amino-3,5-dibromo-N-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)carbonyl]-D-phenylalanyl]-4-(4-fluorophenyl)-piperazine
(133) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(2-methoxyphenyl)-piperazine
(134) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(135) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(136) 1-[N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(137) 1-[4-Amino-N-[[4-(1H-benzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(138) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3(2H)-dioxo-1H-isoindol-2-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(139) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(140) 1-[N2-[3,5-Dibromo-N-[[4-(2,4(1H,3H)-dioxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(141) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(142) 1-[N2-[3,5-Dibromo-N-[[4-(2,4(1H,3H)-dioxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(143) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(144) 1-[3,5-Dibromo-N-[(4xe2x80x2(3xe2x80x2H)-oxospiro[piperidine-4,2xe2x80x2(1xe2x80x2H)-quinazolin]-1-yl)carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(145) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(146) 1-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D,L-3-(4-pyridinyl)alanyl]-4-(4-pyridinyl)-piperazine
(147) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(148) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(149) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(150) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-5-(methoxycarbonyl)-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(151) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-5-(hydroxycarbonyl)-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(152) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxomidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(153) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-5-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(154) 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(155) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-fluorophenyl)-piperazine
(156) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(2-fluorophenyl)-piperazine
(157) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-fluorophenyl)-piperazine
(158) 1-[4-Amino-3,5-dibromo-N-[[4-(phenylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(159) 1-(4-Amino-3,5-dibromo-N-[[4-[N-(aminocarbonyl)-N-phenylamino]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(160) 1-[3,5-Dibromo-N-[[4-(aminocarbonylamino)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
161) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-4-pyrimidinyl)-piperazine
(162) 1-[3,5-Dibromo-N-[[4-[2(3H)-oxobenzoxazol-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(163) 1-[N-[[4-(Aminocarbonylamino)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(164) 1-[4-Amino-3,5-dibromo-N-[[4-(phenylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(165) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyrimidinyl)-piperazine
(166) 1-[3,5-Dibromo-N-[[4-(methylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(167) 1-[3,5-Dibromo-N-[[4-[N-(aminocarbonyl)-methylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(168) 1-[N2-[N-[[4-(Aminocarbonylamino)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperidine
(169) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(3-pyridinyl)-piperazine
(170) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(3-pyridinyl)-piperazine
(171) 1-[3,5-Dibromo-N-[[4-(phenylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(172) 1-[3,5-Dibromo-N-[[4-(phenylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(173) 1-[2,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(4-pyridinyl)-piperidine
(174) 1-[2,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(4-pyridinyl)-piperazine
(175) 1-[3,5-Dibromo-N-[[4-[N-(aminocarbonyl)-N-phenylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(176) 1-[N2-[3,5-Dibromo-N-[[4-(methylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperidine
(177) 1-[N2-[3,5-Dibromo-N-[[4-[N-(aminocarbonyl)methylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperidine
(178) 1-[3,5-Dibromo-N-[[4-[N-(methylaminocarbonyl)-methylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(179) 1-[N2-[N-[[4-(Aminocarbonylamino)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(180) 1-[N2-[3,5-Dibromo-N-[[4-[N-(methylaminocarbonyl)methylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperidine
(181) 1-[N2-[3,5-Dibromo-N-[[4-[N-(aminocarbonyl)methylaminol-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(182) 1-[N2-[3,5-Dibromo-N-[[4-[N-(methylaminocarbonyl)amino]-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(183) 1-[N2-[3,5-Dibromo-N-[[4-[N-(methylaminocarbonyl)methylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(184) 1-[N2-[N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(185) 1-[N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(186) 1-[N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(187) 1-[N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(188) 1-[N2-[N-[[4-[2(3H)-Oxobenzoxazol-3-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(189) 1-[4-Amino-3,5-dibromo-N-[[4-(1H-indol-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(190) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(191) 1-[N2-[2,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(192) 1-[N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(193) 1-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-phenylpiperazine
(194) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-cyclohexyl-4-piperidinyl)-piperazine
(195) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(1-piperidinyl)-piperidine
(196) 1-[N2-[N-[[4-(2-Cyanophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(1-piperidinyl)-piperidine
(197) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(198) 1-[N2-[N-[[4-(2-Cyanophenyl)-1-piperazinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(199) 1-[3,5-Dichloro-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(200) 1-[3,5-Dichloro-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(201) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-6-hydroxy-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(202) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-morpholinyl)-piperidine
(203) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(ethoxycarbonyl)-piperidine
(204) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(dimethylamino)-piperidine
(205) 1-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(206) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-pyrrolidinyl)-piperidine
(207) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(methoxycarbonyl)-4-phenylpiperidine
(208) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-L-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(209) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-L-tyrosyl]-D-lysyl]-4-(4-pyridinyl)-piperazine
(210) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-D-lysyl]-4-(4-pyridinyl)-piperazine
(211) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(hydroxycarbonyl)-piperidine
(212) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6,N6-dimethyl-L-lysyl]-4-(4-pyridinyl)-piperazine
(213) 1-[N2-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(214) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-piperidinyl)-piperazine
(215) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-piperidine
(216) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-b]pyridin-3-yl)-piperidine
(217) 1-[N2-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(218) 1-[N2-[3-Bromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(219) (R)-1-[2-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-N-methylamino]-3-(3,5-dibromo-4-hydroxyphenyl)-propyl]-4-(1-piperidinyl)-piperidine (220) (R)-1-[2-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]amino]-3-(3,5-dibromo-4-hydroxyphenyl)-propyl]-4-(1-piperidinyl)-piperidine
(221) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-N6,N6-dimethyl-L-lysyl]-4-(4-pyridinyl)-piperazine
(222) 3,5-Dibromo-N2-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-N-[(2-[4-(1-piperidinyl)-1-piperidinyl]ethyl]-D-tyrosinamide
(223) 1-[3,5-Dibromo-N-[[4-[5-[(4-morpholinyl)carbonyl]-1,3-dihydro-2(2H)-oxobenzimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(224) 1-[3,5-Dibromo-N-[[4-[5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-dihydro-2(2H)-oxobenzimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(225) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(226) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(227) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquiazolin-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(228) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(229) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxoimidazo[4,5-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(230) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(231) 1-[4-Amino-3,5-dibromo-N-[[4-(2,3,4,5-tetrahydro-2(1H)-oxo-1,3-benzodiazepin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(232) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(233) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(234) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(235) 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(236) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(237) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(238) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(239) 1-(3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(240) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(241) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(242) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(243) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(244) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperazine
(245) (R)-1-[2-[N-[[4-(3,4-dihydro-2(1H)-oxopyrido[2,3-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]amino]-3-(4-amino-3,5-dibromophenyl)-propyl]-4-(1-piperidinyl)-piperidine
(246) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-(1,3-dihydro-2(2H)oxobenzimidazol-1-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(247) 1-[N2-[2,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperidine
(248) 1-[N2-[3,5-Dibromo-N-[[4-[2(3H)-oxobenzoxazol-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(249) 1-[N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-4-amino-3,5-dibromo-D-phenylalanyl]-4-[(1-piperidinyl)methyl]-piperidine
(250) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(251) 1-[N2-[2,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(252) 1-[N2-[2,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-L-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(253) 1-[N2-[2,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(254) 1-[N2-[3,5-Dibromo-N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(255) 1-[N2-[3,5-Dibromo-N-[[4-[N-(Aminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(256) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(257) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-glycyl]-4-(4-pyridinyl)-piperazine
(258) 1-[4-Amino-3,5-dibromo-N-[[4-(benzoylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(259) 1-[4-Amino-3,5-dibromo-N-[[4-(benzoylaminocarbonylamino)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(260) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-xcex2-alanyl]-4-(4-pyridinyl)-piperazine
(261) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-N-methylglycyl]-4-(4-pyridinyl)-piperazine
(262) 1-[4-Amino-3,5-dibromo-N-[[4-[N-(phenylaminocarbonyl)-phenylamino)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(263) 1-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-[3-(2-thienyl)-D-alanyl]-4-(1-piperidinyl)-piperidine
(264) 4-Amino-3,5-dibromo-N2-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-N-methyl-N-[3-(4-methyl-1-piperazinyl)propyl]-D-phenylalaninamide
(265) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-glycyl]-4-(1-piperidinyl)-piperidine
(266) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-alanyl]-4-(4-pyridinyl)-piperazine
(267) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-[N-(methylaminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-D-phenylalanyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(1-piperidinyl)-piperidine
(268) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-alanyl]-4-(1-piperidinyl)-piperidine
(269) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperazinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(270) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperazinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(271) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-[N-(methylaminocarbonyl)phenylamino]-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(1-piperidinyl)-piperidine
(272) 1-[N2-[[4-(1,3-Dihydro-2(2H)oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-1-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-(1-piperidinyl)-piperidine
(273) 1-[N-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-N-methylglycyl]-4-(1-piperidinyl)-piperidine
(274) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinoxalin-3-yl]-1-piperazinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(275) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinoxalin-3-yl]-1-piperazinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(276) 1-[4-Amino-3,5-dibromo-N-[[4-[N-(aminocarbonyl)-N-(4-fluorophenyl)amino]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(277) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-4-methyl-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(278) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-4-methyl-1-piperidinyl]carbonyl]-D-phenylalanyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperidine
(279) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[3-dimethylamino)propyl]-piperidine
(280) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-4-methyl-1-piperidinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(281) 1-[N-[[4-(1,3-Dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tryptyl]-4-(1-piperidinyl)-piperidine
(282) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)l-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(283) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperazinyl]carbonyl]-D-phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine
(284) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(285) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(4-pyridinyl)-piperidine
(286) 3,5-Dibromo-N2-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-N-[2-(4-methyl-1-piperazinyl)ethyl]-D-tyrosinamide
(287) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(288) 1-[3,5-Dibromo-N-[[4-(7,9-dihydro-6,8-dioxo-1H-purin-9-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(289) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(290) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(4-pyridinyl)-piperidine
(291) (R,S)-1-[2-(4-Amino-3,5-dibromobenzoyl)-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-4-oxobutyl]-4-(4-pyridinyl)-piperidine
(292) (R)-1-[3-(3,5-Dibromo-4-hydroxyphenyl)-2-[N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(293) 1-[N6-Acetyl-N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(294) 1-[N2-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-N6,N6-dimethyl-L-lysyl]-4-(4-pyridinyl)-piperazine
(295) 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6,N6-dimethyl-L-lysyl]-4-(4-pyridinyl)-piperazine
(296) (R,S)-1-[2-(4-Amino-3,5-dibromobenzoyl)-4-[4-(3,4-dihydro-2((1H)-oxoquinazolin-3-yl)-1-piperidinyl]-4-oxobutyl]-4-(1-piperidinyl)-piperidine
(297) (R)-1-[3-(4-Amino-3,5-dibromophenyl)-2-[N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(298) (R)-1-[3-(4-Amino-3-bromophenyl)-2-[N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(299) (R)-1-[3-(4-Amino-3,5-dibromophenyl)-2-[N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(300) (R)-1-[3-(4-Amino-3-bromophenyl)-2-[N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(301) (R)-1-[3-(3,5-Dibromo-4-hydroxyphenyl)-2-[N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(302) (R,S)-1-[2-(4-Amino-3,5-dibromobenzoyl)-4-[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]-4-oxobutyl]-4-(1-piperidinyl)-piperidine
(303) 1-[4-Amino-N-[[4-[2-(aminocarbonylamino)phenylamino]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(304) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-7-(methoxycarbonyl)-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(305) 1-[4-Amino-N-[[4-[2-(methylsulphonylamino)phenylamino]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(306) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-7-(hydroxycarbonyl)-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(307) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-7-(methoxycarbonyl)-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(308) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4,4a,5,6,7,8,8a-octahydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(309) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-7-(hydroxycarbonyl)-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(310) 1-[4-Amino-N-[[4-[7-(aminocarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(311) 1-[4-Amino-3,5-dibromo-N-[[4-[7-(2-hydroxyethylaminocarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(312) 1-[4-Amino-N-[[4-[7-(aminocarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(313) 1-[4-Amino-3,5-dibromo-N-[[4-[7-(2-hydroxyethylaminocarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(314) 1-[4-Amino-3,5-dibromo-N-[[4-(1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(315) 1-[4-Amino-3,5-dibromo-N-[[4-(1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(316) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(317) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-fluorophenyl)-piperazine
(318) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-fluorophenyl)-piperazine
(319) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-fluorophenyl)-piperazine
(320) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-fluorophenyl)-piperazine
(321) 1-[3,5-Dibromo-N-[[4-(1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(322) trans-1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-cyclohexyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(323) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-6,7-dimethoxy-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(324) 1-[N-[[4-(5-Chloro-3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(325) 1-[3,5-Dibromo-N-[[3-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-pyrrolidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(326) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(327) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(328) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-8-methoxy-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(329) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-(4-methoxyphenyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(330) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-(4-methoxyphenyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(331) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-(4-methoxyphenyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(332) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(333) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(334) 1-[N-[[4-(1,3-dihydro-4-[3-(trifluoromethyl)-phenyl]-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-3-(4-pyridinyl)-D,L-alanyl]-4-(4-pyridinyl)-piperazine
(335) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(336) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(337) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(338) (R)-1-[3-(4-Amino-3,5-dibromophenyl)-2-[N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(339) (R)-1-[3-(4-Amino-3,5-dibromophenyl)-2-[N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]amino]propyl]-4-(1-piperidinyl)-piperidine
(340) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperidine
(341) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1methyl-4-piperidinyl)-piperidine
(342) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-(3-thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(343) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-(3-thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperidine
(344) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(345) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(346) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(347) 1-[4-Amino-3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(348) 1-[4-Amino-3,5-dibromo-N-[[4-(2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(349) 1-[4-Amino-3,5-dibromo-N-[[4-(2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(350) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(351) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(352) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(353) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-(3-thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(354) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D,L-tyrosyl]-4-(4-pyridinyl)-piperidine
(355) 1-[4-Amino-3,5-dibromo-N-[[4-(2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(356) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(357) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-(3-thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(358) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperazine
(359) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(360) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(361) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(362) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(363) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(364) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(365) 1-[N2-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(366) 1-[4-Amino-3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperidine
(367) 1-[4-Amino-3,5 dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperidine
(368) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperidine
(369) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[4-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperazine
(370) 1-[4-Amino-3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperazine
(371) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperazine
(372) 4-(1-Acetyl-4-piperidinyl)-1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-piperidine
(373) 1-[4-Amino-N-[[4-(6-bromo-3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(374) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-5-methyl-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(375) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(3-nitrophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(376) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(3-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(377) 1-[4-Amino-N-[[4-[4-(3-bromophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(378) 1-[N2-[3,5-Dibromo-N-[[4-(1,3-dihydro-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6-(1,1-dimethylethoxycarbonyl)-L-lysyl]-4-(4-pyridinyl)-piperazine
(379) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-fluorophenyl)-piperazine
(380) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-fluorophenyl)-piperazine
(381) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(3-pyridinyl)-piperazine
(382) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(3-pyridinyl)-piperazine
(383) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(3-pyridinyl)-piperazine
(384) 1-[3,5-Dibromo-N-[[4-[1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(385) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(3-pyridinyl)-piperazine
(386) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(387) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-pyridinyl)-piperazine
(388) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(2-pyridinyl)-piperazine
(389) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(phenylaminocarbonylamino)-piperidine
(390) 1-[4-Amino-3,5-dibromo-N-[[4-[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(391) 1-[3,5-Dibromo-N-[[4-[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(392) 1-[3,5-Dibromo-N-[[4-[4-phenyl-2(1H)-oxopyrimidin-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(393) 4-Cyano-1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-phenylpiperidine
(394) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyrimidinyl)-piperazine
(395) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyrimidinyl)-piperazine
(396) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyrimidinyl)-piperazine
(397) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyrimidinyl)-piperazine
(398) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(399) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine
(400) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(401) 2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indole
(402) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(403) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(404) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-ethylphenyl)-piperazine
(405) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-fluorophenyl)-1,2,5,6-tetrahydropyridine
(406) 1-[3,5-Dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(407) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(408) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(1-oxoethyl)phenyl]-piperazine
(409) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(1-oxoethyl)phenyl]-piperazine
(410) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-fluorobenzoyl)-piperidine
(411) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-cyano-4-phenylpiperidine
(412) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-fluorophenyl)-piperidine
(413) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[(hexahydro-1-methyl-4-pyridinyl)carbonyl]-piperazine
(414) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[3-(dimethylamino)propyl]-piperazine
(415) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[3-(dimethylamino)propyl]-piperazine
(416) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-methyl-1-piperazinyl)-piperidine
(417) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-methyl-1-piperazinyl)-piperidine
(418) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(419) 1-[N-[4-[[1,3-Dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(420) 1-[3,5-Dibromo-N-[[4-[7-(methoxycarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(421) 1-[3,5-Dibromo-N-[[4-[7-(hydroxycarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(422) 1-[3,5-Dibromo-N-[[4-[7-(methoxycarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(423) 1-[3,5-Dibromo-N-[[4-[7-(hydroxycarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(424) 1-[4-Amino-3,5-dibromo-N-[[4-[7-(methylaminocarbonyl)-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(425) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-morpholinyl)-piperidine
(426) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(dimethylamino)-piperidine
(427) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-pyrrolidinyl)-piperidine
(428) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-morpholinyl)-piperidine
(429) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(dimethylamino)-piperidine
(430) 1-[4-Amino-3,5-dibromo-N-[[4-[7-[(4-methyl-1-piperazinyl)carbonyl]-3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(431) 1-[4-Amino-3,5-dibromo-N-[[4-(2,5-dioxo-4-phenylimidazolidin-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(432) 1-[3,5-Dibromo-N-[[4-(2,5-dioxo-4-phenylimidazolidin-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(433) 1-[4-Amino-3,5-dibromo-N-[[4-[2,5-dioxo-4-(phenylmethyl)-imidazolidin-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(434) 1-[3,5-Dibromo-N-[[4-[2,5-dioxo-4-(phenylmethyl)imidazolidin-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(435) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-pyrrolidinyl)-piperidine
(436) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperazine
(437) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(438) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-cyclohexylpiperazine
(439) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-cyclohexylpiperazine
(440) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2,2-dioxido-2,1,3-benzothiadiazin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(441) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2,2-dioxido-2,1,3-benzothiadiazin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(442) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2,2-dioxido-2,1,3-benzothiadiazin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperidine
(443) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperazine
(444) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(445) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-pyridinyl)-piperazine
(446) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperidine
(447) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-pyridinyl)-piperazine
(448) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(449) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(4-fluorophenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(450) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-N-methyl-D-tyrosyl]-4-(4-pyridinyl)-piperidine
(451) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(4-pyridinyl)-piperazine
(452) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(4-pyridinyl)-piperazine
(453) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperazine
(454) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(455) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(456) 1-[3,4-Dichloro-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(457) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(4-pyridinyl)-piperidine
(458) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(459) (R,S)-1-[2-[(3,5-Dibromo-4-hydroxyphenyl)methyl]-4-[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-1,4-dioxobutyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(460) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-cycloheptylpiperazine
(461) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-cyclopentylpiperazine
(462) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-4-methoxy-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(463) 1-[3,5-Bis-(trifluoromethyl)-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(4-pyridinyl)-piperazine
(464) 1-[3,5-Bis-(trifluoromethyl)-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(465) 1-[3,5-Bis-(trifluoromethyl)-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(466) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(4-biphenylyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(467) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(2-naphthyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(468) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(2-naphthyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(469) 1-[3-Bromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(470) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(4-biphenylyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(471) 1-[N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(4-biphenylyl)-D,L-alanyl]-4-(1-piperidinyl)-piperidine
(472) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-biphenylyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(473) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-(2-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(474) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(2-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(475) 1-[3,5-Bis-(trifluoromethyl)-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(476) 1-[3,5-Bis-(trifluoromethyl)-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(477) 1-[3,4-Dichloro-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(4-pyridinyl)-piperazine
(478) 1-[3-Bromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(479) 1-[3-Bromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(480) 1-[3-Bromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(4-pyridinyl)-piperidine
(481) 1-[4-Amino-3,5-dibromo-N-[[4-[4-(3,4-dichlorophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(482) 1-[4-Amino-3,5-dibromo-N-[[4-[4-(3,4-dichlorophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(483) 1-[4-Amino-N-[[4-[4-(3-chlorophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(484) 1-[4-Amino-N-[[4-[4-(3-chlorophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(485) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-benzoyl-4-piperidinyl)-piperidine
(486) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methylsulphonyl-4-piperidinyl)-piperidine
(487) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[1-(3-carboxy-1-oxopropyl)-4-piperidinyl]-piperidine
(488) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-hexyl-4-piperidinyl)-piperidine
(489) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-cyclopropylmethyl-4-piperidinyl)-piperidine
(490) 1-[3,5-Dibromo-N-[[4-(2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperidine
(491) 1-[3,5-Dibromo-N-[[4-(2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(492) 1-[3,5-Dibromo-N-[[4-(2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-piperazine
(493) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[1-(ethoxycarbonylmethyl)-4-piperidinyl]-piperidine
(494) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[1-(carboxymethyl)-4-piperidinyl]-piperidine
(495) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4,5-diphenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(496) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[(4-pyridinyl)carbonyl]-piperazine
(497) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-methyl-1-piperazinyl)piperidine
(498) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)piperidine
(499) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)piperidine
(500) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[(1-methyl-4-piperidinyl)carbonyl]-piperazine
(501) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-methyl-1-piperazinyl)piperidine
(502) 1-[3,5-Dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)piperidine
(503) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)piperidine
(504) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[(4-methyl-1-piperazinyl)carbonyl]-piperidine
(505) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)carbonyl]-piperidine
(506) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(507) 1-[3-Chloro-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(508) (R,S)-1-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]-2-[[3-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(509) 1-[4-Amino-3,5-dibromo-N-[[4-[4-(3-bromophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(510) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-(3-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(511) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-methoxy-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(512) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-methoxy-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(513) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-methoxy-D,L-phenylalanyl]-4-(4-pyridinyl)-piperazine
(514) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-methoxy-D,L-phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(515) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-methoxy-D,L-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperazine
(516) 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-L-tyrosyl]-D-lysyl]-4-(4-pyridinyl)-piperazine
(517) 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-D-lysyl]-4-(4-pyridinyl)-piperazine
(518) 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-L-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
(519) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-(3-hydroxyphenyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(520) 1-[4-Amino-N-[[4-[4-[3,5-bis-(trifluoromethyl)phenyl]-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(521) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-piperidinyl)-piperidine
(522) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-piperidinyl)-piperidine
(523) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-4-(methylsulphonyloxy)-D-phenylalanyl]-4-[1-(methylsulphonyl)-4-piperidinyl]-piperidine
(524) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-(methylsulphonyl)-4-piperidinyl]-piperidine
(525) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-(cyclopropylmethyl)-4-piperidinyl]-piperidine
(526) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-(hydroxycarbonylmethyl)-4-piperidinyl]-piperidine
(527) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-(2-methyl-4-thiazolyl)-D,L-alanyl]-4-(1-piperidinyl)-piperidine
(528) 1-[N-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-3-(2-methyl-4-thiazolyl)-D,L-alanyl]-4-(4-pyridinyl)-piperazine
(529) (R,S)-1-[2-[(1-Naphthyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(530) (R,S)-1-[2-[(1-Naphthyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(531) (R,S)-1-[2-[(3-Methoxyphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(532) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-ethenyl-D,L-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(533) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(534) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(535) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperazinyl)-piperidine
(536) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxopyrido[4,3-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(537) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxopyrido[4,3-d]pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-piperidine
(538) (R,S)-1-[2-[(1-Naphthyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(539) (R,S)-1-[2-[(1-Naphthyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperazinyl)-piperidine
(540) (R,S)-1-[2-[(1-Naphthyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(541) (R,S)-1-[2-[(3-Ethoxyphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperazinyl)-piperidine
(542) (R,S)-1-[2-[(3-Ethoxyphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(543) (R,S)-1-[2-[(3-Ethoxyphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(544) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(1-methylethoxy)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(545) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(1-methylethoxy)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperazinyl)-piperidine
(546) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(1-methylethoxy)phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(547) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(548) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperazinyl)-piperidine
(549) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(550) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-[2-(dimethylamino)ethoxy]phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperazinyl)-piperidine
(551) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazalin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[(1-methyl-4-piperazinyl)carbonyl]-piperidine
(552) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(1-oxoethyl)-1-piperazinyl]-piperidine
(553) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[4-(1-oxoethyl)-1-piperazinyl]-piperidine
(554) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(1-oxoethyl)-1-piperazinyl]-piperidine
(555) 1-[3,5-Dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[4-(1-oxoethyl)-1-piperazinyl]-piperidine
(556) 1-[4-Amino-3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[(1-methyl-4-piperazinyl)carbonyl]-piperazine
(557) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[(1-methyl-4-piperazinyl)carbonyl]-piperazine
(558) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[(4-pyridinyl)carbonyl]-piperazine
(559) 1-[4-Amino-3,5-dibromo-N-[(4-oxo-1-piperidinyl)carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(560) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-[4-(dimethylamino)butyl]phenyl]-piperazine
(561) 1-[4-Amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-[4-(dimethylamino)butyl]phenyl]-piperazine
(562) 1-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[(1-methyl-4-piperazinyl)carbonyl]-piperazine
(563) 1-[3,5-Dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[(1-methyl-4-piperazinyl)carbonyl]-piperazine
(564) 1-[4-Amino-N-[(4-amino-1-piperidinyl)carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(565) 1-[4-Amino-3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(566) 1-[4-Amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(567) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(4-methyl-1-piperazinyl)-piperidine
(568) 1-[4-Amino-3,5-dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(569) 1-[3,5-Dibromo-N-[[4-[2(1H)-oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-methyl-1-piperazinyl)-piperidine
(570) 1-[N2-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-methyl-D-tryptyl]-4-(1-methyl-4-piperidinyl)-piperidine
(571) 1-[N2-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-methyl-D-tryptyl]-4-(4-methyl-1-piperazinyl)-piperidine
(572) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-methyl-D-tryptyl]-4-(1-methyl-4-piperidinyl)-piperidine
(573) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-methyl-D-tryptyl]-4-(4-methyl-1-piperazinyl)-piperidine
(574) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(575) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(576) 1-[N2-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-(4-methyl-1-piperazinyl)-piperidine
(577) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-(4-methyl-1-piperazinyl)-piperidine
(578) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromophenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(579) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromophenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(580) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-(1-methyl-4-piperidinyl)-piperidine
(581) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-(1-methyl-4-piperidinyl)-piperidine
(582) 1-[4-Amino-3,5-dibromo-N-[[4-(2,3-dihydro-4(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(583) 1-[N2-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-methyl-D-tryptyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(584) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-methyl-D-tryptyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(585) 1-[4-Amino-N-[[4-[4-(4-amino-3,5-dibromophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(1-piperidinyl)-piperidine
(586) 1-[4-Amino-N-[[4-[4-(4-amino-3,5-dibromophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-dibromo-D-phenylalanyl]-4-(4-methyl-1-piperazinyl)-piperidine
(587) 1-[N2-[[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(588) 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-Nxe2x80x2-(1,1-dimethylethoxycarbonyl)-D-tryptyl]-4-[4-(dimethylamino)-1-piperidinyl]-piperidine
(589) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromo-4-methylphenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(590) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromo-4-methylphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(591) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3,4-difluoro-5-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(592) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3,4-difluoro-5-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(593) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-4-(ethoxycarbonyl)-piperidine
(594) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-4-(ethoxycarbonylmethyl)-piperidine
(595) (R,S)-2-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-6-methyl-2,6-diazaspiro[3,4]octane
(596) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-4-(hydroxycarbonylmethyl)-piperidine
(597) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[1-methyl-1H-indol-3-yl]methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(598) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[1-methyl-1H-indol-3-yl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(599) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-(ethoxycarbonyl)-2-[[1-methyl-1H-indol-3-yl]methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(600) (R,S)-1-[4-[4-(Aminocarbonylamino)-1-piperidinyl]-2-[[1-methyl-1H-indol-3-yl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(601) (R,S)-1-[4-[4-(Aminocarbonylamino)-1-piperidinyl]-2-(ethoxycarbonyl)-2-[[1-methyl-1H-indol-3-yl]methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(602) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromo-4-methoxyphenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(603) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dichlorophenyl)methyl]-1,4-dioxobutyl]-4-carboxypiperidine
(604) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromo-4-methoxyphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(605) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[4-fluor-3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(607) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[4-fluor-3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(607) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperazine
(608) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine
(609) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(610) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(4-pyridinyl)-piperazine
(611) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(trifluoromethyl)-D,L-phenylalanyl]-4-(4-pyridinyl)-piperidine
(612) (R,S)-1-[2-[(4-Amino-3,5-dibromophenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(613) 1-[3-Chloro-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(614) 1-[3-Chloro-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(615) 1-[3-Chloro-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(cyclopentyl)-piperazine
(616) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3-methylphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(617) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(hexahydro-1H-1-azepinyl)-piperidine
(618) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-piperazine
(619) 1-[3-Bromo-N-[[4-(1,3-dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(620) 1-[3-cyano-N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(621) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-methyl-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(622) 1-[N-[[4-(1,3-Dihydro-4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-3-methyl-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(623) 1-[3-Methyl-N-[[4-[3,4-dihydro-2(1H)-oxothieno[3,4-d]-pyrimidin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(624) 1-[N-[[4-[1,3-Dihydro-4-(3-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3-methyl-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(625) 1-[N-[[4-[1,3-Dihydro-4-[(3-(trifluoromethyl)-phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3-methyl-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(626) 1-[3-Bromo-N-[[4-[1,3-dihydro-4-[(3-(trifluoromethyl)-phenyl]-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(627) 1-[3-Bromo-N-[[4-[3,4-dihydro-2(1H)-oxothieno[3,4-d]-pyrimidin-3-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(628) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(629) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperazine
(630) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)-phenyl]methyl]-1,4-dioxobutyl]-4-(4-pyridinyl)-piperazine
(631) (R,S)-4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-4-oxo-2-[[3-(trifluoromethyl)-phenyl]methyl]-N-[2-(4-methyl-1-piperazinyl)ethyl]-butanamide
(632) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-(1H-tetrazol-5-yl)-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(633) 1-[3-Bromo-N-[[4-[1,3-dihydro-4-(3-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D,L-phenylalanyl]-4-(1-piperidinyl)-piperidine
(634) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(2-naphthyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(635) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[2-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(636) 1-[N-[[4-[3,4-Dihydro-2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-3-nitro-D,L-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine
(637) (R,S)-1-[2-[(4-Amino-3,5-dibromophenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(638) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[2-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(639) (R,S)-1-[2-[[3,5-Bis-(trifluoromethyl)phenyl]methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(640) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dimethoxyphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(641) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(2-naphthyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(642) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dimethoxyphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(643) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(4-piperidinyl)-piperidine
(644) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(645) (R,S)-1-[2-[(3-Bromophenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(646) (R,S)-1-[2-[(3-Bromophenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(647) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(1-propen-3-yl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(648) (R,S)-1-[2-[3-(Biphenylyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(649) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(pyridinyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(650) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(2-thiazolyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(651) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[3-(2-furyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(652) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3-propylphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(653) (R,S)-1-[4-(2,4-Dihydro-5-phenyl-3(3H)-oxotriazol-2-yl)-1-piperidinyl]-2-[[3-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(654) (R,S)-1-[4-[1,3-Dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl]-1-piperidinyl]-2-[[3-(trifluoromethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(655) (R,S)-1-[2-[(4-Quinolinyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(656) (R,S)-1-[2-[(4-Quinolinyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(657) 1-[2-[(1,2,3,4-Tetrahydro-1-naphthyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine (mixture of diastereomers)
(658) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dibromophenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(659) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-dibromophenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(660) (R,S)-1-[2-[(4-Quinolinyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(661) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-hydroxy-3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(662) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-hydroxy-3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(663) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-hydroxy-3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(664) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-methoxy-3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-piperidine
(665) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-methoxy-3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(666) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-methoxy-3,5-dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(667) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(1-naphthyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-piperazinyl)-piperidine
(668) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[(1-naphthyl)methyl]-1,4-dioxobutyl]-4-(1-methylsulphonyl-4-piperidinyl)-piperidine
(669) (R,S)-1-[2-[3,5-Dibromo-4-methylphenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-[4-[4-(dimethylamino)butyl]phenyl]-piperazine
(670) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[4-(1,1-dimethylethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(671) (R,S)-1-[4-[4-(3,4-Dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[4-(1,1-dimethylethyl)phenyl]methyl]-1,4-dioxobutyl]-4-(1-methyl-4-piperidinyl)-piperidine
(672) (R,S)-1-[2-[(3,4-Dichlorophenyl)methyl]-4-[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-1,4-dioxobutyl]-4-[4-(dimethylaminomethyl)phenyl]-piperidine
and the salts thereof.
The compounds of general formula I are prepared by methods which are known in principle, particularly using processes derived from peptide chemistry (cf. for example Houben-Weyl, Methoden der Organischen Chemie, Vol. 15/2). The amino protecting groups used may be those described in Houben-Weyl, Methoden der Organischen Chemie, Vol. 15/1, of which urethane protecting groups such as the fluorenylmethoxycarbonyl, phenylmethoxycarbonyl or tert.-butyloxycarbonyl group are preferred. Any functional groups present in the groups R2 and/or A of the compounds of general formula I or in the precursors thereof are additionally protected by suitable protecting groups in order to prevent side reactions (cf. for example: G. B. Fields et al., Int. J. Peptide Protein Res. 35, 161 (1990); T. W. Greene, Protective Groups in Organic Synthesis). Examples of side-chain-protected amino acids of this kind include, in particular, Arg(NO2), Arg(Mtr), Arg(di-Z), Arg(Pmc) Lys(Boc), Lys(Z), Orn(Boc), Orn(Z), Lys(Cl-Z) which are commercially obtainable, possibly in the form of derivatives. Particular care should be taken to ensure that so-called orthogonal combinations of protecting groups are used to protect the xcex1-amino and the side chain amino group, e.g.:
Instead of protecting amino groups in the side chain, amino acids or derivatives thereof which carry precursor functions and in particular are substituted by nitro or cyano in the side chain, such as 5-o-cyanonorvalin may also be used.
The basic functions in the side chains of xcex1-amino acids which are not commercially obtainable and which are characterised, for example, by (aminoiminomethyl) groups, may be protected in the same way as is used for protecting the side chains of arginine and its derivatives (cf. also M. Bodanszky, xe2x80x9cPeptide Chemistryxe2x80x9d, Springer-Verlag, 1988, p. 94-97); protecting groups which are particularly suitable for the (aminoiminomethyl)- group are the p-toluenesulphonyl, mesitylene sulphonylxe2x80x94(Mts), methoxytrimethylphenylsulphonylxe2x80x94(Mtr), 2,2,5,7,8-pentamethylchroman-6-sulphonylxe2x80x94(Pmc), pentachlorophenoxycarbonyl- and nitro-protecting groups.
For the actual coupling, the methods known from peptide chemistry are used (see Houben-Weyl, for example, Methoden der Organischen Chemie, Vol. 15/2). It is preferable to use carbodiimides such as dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) or ethyl-(3-dimethylaminopropyl)-carbodiimide, O-(1H-benzotriazol-1-yl)N,N-Nxe2x80x2,Nxe2x80x2-tetramethyluroniumhexafluorophosphate (HBTU) or tetrafluoroborate (TBTU) or 1H-benzotriazol-1-yloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP). By the addition of 1-hydroxybenzotriazole (HOBt) or 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOObt) racemisation may additionally be suppressed, if desired, or the reaction rate may be increased. The couplings are normally carried out with equimolar amounts of the coupling components and the coupling reagent in solvents such as dichloromethane, tetrahydrofuran, acetonitrile, dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone (NMP) or mixtures thereof and at temperatures between xe2x88x9230 and +30xc2x0 C., preferably between xe2x88x9220 and +20xc2x0 C. If necessary, N-ethyl-diisopropylamine (DIEA) is preferred as an additional auxiliary base (Hxc3xcnig base).
The so-called xe2x80x9canhydride methodxe2x80x9d (cf. also M. Bodanszky, xe2x80x9cPeptide Chemistryxe2x80x9d, Springer-Verlag 1988, p. 58-59; M. Bodanszky, xe2x80x9cPrinciples of Peptide Synthesisxe2x80x9d, Springer-Verlag 1984, p. 21-27) was used as another coupling method for the synthesis of compounds of general formula I. The xe2x80x9cmixed anhydride methodxe2x80x9d is preferred, in the variant according to Vaughan (J. R. Vaughan Jr., J. Amer. Chem.Soc. 73, 3547 (1951)), in which the mixed anhydride is obtained from the optionally N2-protected xcex1-amino acid which is to be coupled, and the mono-isobutylcarbonate, using isobutylchlorocarbonate in the presence of base such as 4-methylmorpholine or 4-ethylmorpholine. The preparation of this mixed anhydride and the coupling with amines are carried out in a one-pot process using the above-mentioned solvents at temperatures between xe2x88x9220 and +20xc2x0 C., preferably between 0 and +20xc2x0 C.
Any protecting groups present in the side chains of xcex1-amino acid partial structures are finally cleaved, after the formation of the N- and C-terminally substituted amino acid derivative, with suitable reagents which are also known from the literature in principle, specifically arylsulphonyl and hetarylsulphonyl protecting groups, preferably by acidolysis, i.e. by the action of strong acids, preferably trifluoroacetic acid, nitro- and arylmethoxycarbonyl protecting groups are preferably cleaved by hydrogenolysis, e.g. using hydrogen in the presence of palladium black and with glacial acetic acid as solvent. If the substrate contains functions which are sensitive to hydrogenolysis, e.g. halogen atoms such as chlorine, bromine or iodine, a phenylmethanol or hetarylmethanol function or some other benzyl heteroatom bond, particularly a benzyl-oxygen bond, the nitro group may also be cleaved non-hydrogenolytically, e.g. with zinc/2N trifluoroacetic acid (cf. also A. Turan, A. Patthy and S. Bajusz, Acta Chim. Acad. Sci. Hung, Tom. 85 (3), 327-332 [1975]; C.A. 83, 206526y [1975]), with tin(II)-chloride in 60% aqueous formic acid (see also: SUNSTAR KK, JA-A-3271-299), with zinc in the presence of acetic acid (cf. also: A. Malabarba, P. Ferrari, G. Cietto, R. Pallanza and M. Berti, J. Antibiot. 42 (12), 1800-1816 (1989)) or excess aqueous 20% titanium(III)-chloride in aqueous methanol and in the presence of aqueous ammonium acetate buffer at 24xc2x0 C. (see also: R. M. Freidinger, R. Hirschmann and D. F. Veber, J. Org. Chem. 43 (25), 4800-4803 [1978]).
Any precursor functions which may be present in the side chain of the xcex1-amino acid may also subsequently be converted by hydrogenolysis into the desired amino functions; nitroalkyl groups yield aminoalkyl groups under conditions which will be familiar to the chemist, whilst the cyano group is converted into the aminomethyl group.
Alternatively, nitrile functions may also be reduced with complex hydrides which are selective in relation to other critical functions contained in the molecule, particularly amide groups (cf. also: J. Seyden-Penne, xe2x80x9cReductions by the Alumino- and Borohydrides in Organic Synthesisxe2x80x9d, VCH Publishers Inc., 1991, p. 132ff.), e.g. with sodium borohydride in methanol and in the presence of cobalt(II)-chloride, with sodium borohydride in tetrahydrofuran in the presence of trifluoroacetic acid or with tetrakis-(n-butyl)-ammonium borohydride in dichloromethane; the reduction of aliphatic nitro function to the primary amino-function is also possible with sodium borohydride in the presence of tin(II)-chloride or copper(II)-acetylacetonate, without affecting the carboxamide groups present in type I compounds (see also: J. Seyden-Penne, ibid. p. 137ff.).
The following methods are particularly suitable for preparing the compounds of general Formula I according to the invention:
a) In order to prepare compounds of general formula I, wherein
R denotes an unbranched C1-7-alkyl group which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group, by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or biphenylyl group,
by a 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-2H-2-oxoimidazopyridinyl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 1,3-dihydro-2H-2-oxoimidazol-1-yl or 3,4-dihydro-2(1H)-oxopyrimidin-3-yl group, wherein the latter two groups may each be mono- or disubstituted in the 4- and/or 5-position or in the 5- and/or 6-position by lower straight chained or branched alkyl groups, by phenyl, biphenylyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl-1-methylpyrazolyl, imidazolyl- or 1-methylimidazolyl-groups and the substituents may be identical or different,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group,
or by a 6-membered heteroaromatic ring linked via a carbon atom, which contains one, two or three nitrogen atoms,
whilst a 1,4-butadienylene group may be attached both to the above-mentioned 5-membered heteroaromatic monocyclic rings and to the 6-membered heteroaromatic monocyclic rings, in each case via two adjacent carbon atoms, and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group, and
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl groups in the xcfx89-position and optionally also partially hydrogenated mono- and bi-cyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms or by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, wherein the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino and benzoylmethylamino groups may in turn additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group,
or the group of formula 
xe2x80x83wherein
R5, R6, R7, RN, Y1, o and p are as hereinbefore defined,
Y2 denotes a CHxe2x80x94 group and
Z denotes an NR1xe2x80x94 group, wherein R1 is as hereinbefore defined:
coupling carboxylic acids of general formula VII,
RCO2Hxe2x80x83xe2x80x83(VII)
wherein
R is as hereinbefore defined,
with compounds of general formula VIII, 
xe2x80x83wherein
R2, R3, R4, R11, A, X, m and n are as hereinbefore defined, and
Z denotes an NR1xe2x80x94 group, wherein R1 is as hereinbefore defined, and, if necessary, subsequently cleaving any protecting groups or modifying precursor functions in accordance with the methods described hereinbefore.
The coupling is carried out using the methods known from peptide chemistry described above, particularly using DCC, DIC, HBTU, TBTU or BOP as reagents or using the mixed anhydride method.
b) In order to prepare compounds of general formula I wherein R is defined as in a), Z denotes the NR1xe2x80x94 group and R1, R2, R3, R4, R11, A, X, m and n are as hereinbefore defined:
coupling compounds of general formula IX,
Rxe2x80x94COxe2x80x94Nuxe2x80x83xe2x80x83(IX)
wherein
R is defined as in a) and
Nu denotes a leaving group, for example a halogen atom such as the chlorine, bromine- or iodine atom, an alkylsulphonyloxy group having 1 to 10 carbon atoms in the alkyl moiety, a phenylsulphonyloxy or naphthylsulphonyloxy group optionally mono-, di- or trisubstituted by chlorine or bromine atoms or by methyl- or nitro groups, wherein the substituents may be identical or different, a 1H-imidazol-1-yl, a 1H-pyrazol-1-yl- optionally substituted by 1 or 2 methyl groups in the carbon skeleton, a 1H-1,2,4-triazol-1-yl, 1H-1,2,3-triazol-1-yl, 1H-1,2,3,4-tetrazol-1-yl, a vinyl, propargyl, p-nitrophenyl, 2,4-dinitrophenyl, trichlorophenyl, pentachlorophenyl, pentafluorophenyl, pyranyl or pyridinyl, a dimethylaminyloxy, 2(1H)-oxopyridin-1-yloxy, 2,5-dioxopyrrolidin-1-yloxy, phthalimidyloxy, 1H-benzotriazol-1-yloxy or azide group,
with compounds of general formula VIII, 
xe2x80x83wherein
R2, R3, R4, R11, A, X, m and n are as hereinbefore defined and
Z denotes an NR1xe2x80x94 group, whilst R1 is as hereinbefore defined,
and, if necessary, subsequently cleaving protecting groups or modifying precursor functions using the methods described above.
The reaction is carried out under Schotten-Baumann- or Einhorn-conditions, i.e. the components are reacted in the presence of at least one equivalent of an auxiliary base at temperatures between xe2x88x9250xc2x0 C. and +120xc2x0 C., preferably between xe2x88x9210xc2x0 C. and +30xc2x0 C., optionally in the presence of solvents. Auxiliary bases which may be used are preferably alkali- metal and alkaline earth metal hydroxides, e.g. sodium hydroxide, potassium hydroxide or barium hydroxide, alkali metal carbonates, e.g. sodium carbonate, potassium carbonate or cesium carbonate, alkali metal acetate, e.g. sodium- or potassium acetate, as well as tertiary amines, e.g. pyridine, 2,4,6-trimethylpyridine, quinoline, triethylamine, N-ethyl-diisopropylamine, N-ethyl-dicyclohexylamine, 1,4-Diazabicyclo[2,2,2]octane or 1,8-diazabicyclo[5,4,0]undec-7-ene, whilst the solvents which may be used include, for example, dichloromethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, dimethylformamide, dimethylacetamide, N-methyl-pyrrolidone or mixtures thereof; if alkali metal or alkaline earth metal hydroxides, alkali metal carbonates or -acetates are used as auxiliary bases, water may also be added to the reaction mixture as a cosolvent.
c) In order to prepare compounds of general formula I wherein
R denotes an unbranched C1-6-alkylamino group optionally substituted at the nitrogen atom by a C1-6-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl- or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl- or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl-group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl moiety of the alkylamino groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino- or acetylamino group,
or the group of formula 
xe2x80x83wherein
R5, R6, R7, RN, Y1, o and p are as hereinbefore defined,
Y2 denotes the N-atom and
Z denotes the NR1xe2x80x94 group, wherein R1 is as hereinbefore defined:
reacting amines of general formula X
Rxe2x80x94Hxe2x80x83xe2x80x83(X)
wherein
R is as hereinbefore defined, with carbonic acid derivatives of general XI 
xe2x80x83X1 is a nucleofugic group, preferably the 1H-imidazol-1-yl, 1H-1,2,4-triazol-1-yl, trichloromethoxy- or 2,5-dioxopyrrolidin-1-yloxy group,
and with compounds of general formula VIII, 
xe2x80x83wherein
R2, R3, R4, R11, A, X, m and n are as hereinbefore defined and
Z denotes an NR1xe2x80x94 group, wherein R1 is as hereinbefore defined,
and, if necessary, subsequently cleaving any protecting groups or modifying any precursor functions using the method described hereinbefore.
The theoretically two-step reactions are generally carried out as one-pot processes, preferably by reacting one of the two components X or VIII with equimolar amounts of the carbonic acid derivative of general formula XI in a suitable solvent at fairly low temperature, in the first step, and then adding at least equimolar amounts of the other component VIII or X and finishing the reaction at elevated temperature. The reactions with bis-(trichloromethyl)-carbonate are preferably carried out in the presence of at least 2 equivalents (based on bis-(trichloromethyl)-carbonat) of a tertiary base, e.g. triethylamine, N-ethyl-diisopropylamine, pyridine, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane or 1,8-diazabicyclo[5,4,0]undec-7-ene. Examples of solvent, which should be anhydrous, include tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone or acetonitrile, if bis-(trichloromethyl)-carbonate is used as the carbonyl component, anhydrous chlorohydrocarbons such as dichloromethane, 1,2-dichloroethane or trichloroethylene are preferred. The reaction temperatures are between xe2x88x9230 and +25xc2x0 C. for the first step of the reaction, preferably between xe2x88x925 and +10xc2x0 C., and between +15xc2x0 C. and the boiling temperature of the solvent used, preferably between +20xc2x0 C. and +70xc2x0 C. for the second step of the reaction (cf. also: H. A. Staab and W. Rohr, xe2x80x9cSynthesen mit heterocyclischen Amiden (Azoliden)xe2x80x9d, Neuere Methoden der Prxc3xa4parativen Organischen Chemie, Band V, p. 53-93, Verlag Chemie, Weinheim/Bergstr., 1967; P. Majer and R. S. Randad, J. Org. Chem. 59, 1937-1938 (1994); K. Takeda, Y. Akagi, A. Saiki, T. Sukahara und H. Ogura, Tetrahedron Letters 24 (42), 4569-4572 (1983)).
d) In order to prepare compounds of general formula I wherein the carbonyl group linked to the groups R and Z denotes a urea carbonyl group, in which the urea carbonyl is flanked by at least one NHxe2x80x94 group, and wherein
R denotes an unbranched C1-6-alkylamino group optionally additionally substituted at the nitrogen atom by a C1-6-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl- or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl- or 1,3-dihydro-2H-2-oxoimidazom[4,5-b]pyridin-3-yl-group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl moiety of the alkylamino groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group,
or the group of formula 
xe2x80x83wherein
R5, R6, R7, RN, Y1, o and p are as hereinbefore defined and
Y2 denotes the N-atom,
Z denotes the group NR1 and
R1 denotes a hydrogen atom or, provided that, R denotes an unbranched alkylamino group unsubstituted at the nitrogen atom and optionally substituted in the xcfx89-position, R1 may also denote an alkyl or phenylalkyl group:
Reacting amines of general formula Xxe2x80x2,
Rxe2x80x94Hxe2x80x83xe2x80x83(Xxe2x80x2)
wherein R is as hereinbefore defined,
with carbonic acid derivatives of general formula XIxe2x80x2, 
xe2x80x83wherein
X2 denotes a phenoxy group, if X3 is the (1H)-1,2,3,4-tetrazol-1-yl group, the 4-nitrophenoxy group, if X3 is the 4-nitrophenoxy group, and the chlorine atom if X3 is the 2,4,5-trichlorophenoxy group, and with compounds of general formula VIIIxe2x80x2, 
xe2x80x83wherein
R2, R3, R4, R11, X, A, m and n are as hereinbefore defined and
R1 denotes a hydrogen atom or, provided that R is an unbranched alkylamino group unsubstituted at the nitrogen and optionally substituted in the xcfx89-position, R1 may also denote an alkyl or phenylalkyl group, and
if necessary, subsequently cleaving protecting groups or modifying precursor functions using the methods described hereinbefore.
The reactions are in two steps, in principle, with intermediate formation of urethanes, which can be isolated. However, the reactions may also be carried out as one-pot reactions. Preferably, in the first step, one of the two components Xxe2x80x2 or VIIIxe2x80x2 is reacted with equimolar amounts of the carbonic acid derivative of general formula XIxe2x80x2 in a suitable solvent at low temperature, then at least equimolar amounts of the other component VIIIxe2x80x2 or Xxe2x80x2 are added and the reaction is completed at elevated temperature. The reactions are preferably carried out in anhydrous solvents, e.g. in tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, acetonitrile or anhydrous chlorohydrocarbons e.g. dichloromethane, 1,2-dichloroethane or trichloroethylene. The reaction temperatures are between xe2x88x9215 and +40xc2x0 C., preferably between xe2x88x9210 and +25xc2x0 C. for the first step, between +20xc2x0 C. and the boiling temperature of the solvent used, preferably between +20xc2x0 C. and 100xc2x0 C. for the second reaction step (cf. also: R. W. Adamiak and J. Stawinski, Tetrahedron Letters 1977, 22, 1935-1936; A. W. Lipkowski, S. W. Tam and P. S. Portoghese, J. Med. Chem. 29, 1222-1225 (1986); J. Izdebski and D. Pawlak, Synthesis 1989, 423-425).
e) In order to prepare compounds of general formula I wherein Z denotes the group NH and
R denotes an unbranched C1-6-alkylamino group optionally substituted at the nitrogen atom by a C1-6-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group, whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group,
or the group of formula 
xe2x80x83wherein
R5, R6, R7, RN, Y1, o and p are as hereinbefore defined and Y2 denotes an N-atom:
Reacting isocyanates of general formula XII, 
xe2x80x83wherein
R2, R3, R4, R11, A, X, m and n are as hereinbefore defined,
with amines of general formula X,
Rxe2x80x94Hxe2x80x83xe2x80x83(X)
wherein
R is as hereinbefore defined and, if necessary, subsequently cleaving protecting groups or modifying precursor functions using the processes described above.
The reaction is carried out at temperatures between 0xc2x0 C. and 150xc2x0 C., preferably between 20xc2x0 C. and 100xc2x0 C., optionally in the presence of anhydrous solvents, e.g. tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone or 1,3-dimethyl-2-imidazolidinone or mixtures thereof.
f) In order to prepare compounds of general formula I wherein
R denotes an unbranched C1-6-alkylamino group unsubstituted at the nitrogen atom, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl- or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl- or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl-group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkylamino groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl- or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino- and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino- or acetylamino group, and
Z denotes the NR1xe2x80x94 group wherein R1 is as hereinbefore defined:
Reacting isocyanates of general formula XIII,
xe2x80x83Rxe2x95x90Cxe2x95x90Oxe2x80x83xe2x80x83(XIII)
wherein R is as hereinbefore defined, with compounds of general formula VIII, 
wherein R2, R3, R4, R1, A, X, m and n are as hereinbefore defined and
Z denotes an NR1xe2x80x94 group, wherein R1 is as hereinbefore defined,
and, if necessary, subsequently cleaving any protecting groups or modifying the precursor functions using the methods described hereinbefore.
The reaction is carried out at temperatures between 0 and 150xc2x0 C., preferably at temperatures between 20 and 100xc2x0 C., and optionally in the presence of anhydrous solvents, e.g. tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone or 1,3-dimethyl-2-imidazolidinone.
g) In order to prepare compounds of general formula I wherein R, Z, R2, R3, R4, R11, A, m and n have the meanings given hereinbefore and X is as hereinbefore defined, provided that A does not denote a bond or X denotes an oxygen atom, if A denotes a single bond:
Coupling carboxylic acids of general formula XIV, 
xe2x80x83wherein
R, Z, R11, m and n are as hereinbefore defined,
R2xe2x80x2 has the meanings given for R2 hereinbefore or denotes a group R2 substituted by the above-mentioned protecting groups,
Axe2x80x2 has the meanings given for A hereinbefore or, if A denotes the divalent group of an amino acid, it optionally bears in the side chain a precursor group for the group R9, e.g. a cyanopropyl group,
to compounds of general formula XV,
Hxe2x80x94NR3R4xe2x80x83xe2x80x83(XV)
xe2x80x83wherein
R3 and R4 are as hereinbefore defined,
and if necessary subsequent cleaving of protective groups or modification of precursor functions using the methods described above.
The coupling is carried out using the methods known from peptide chemistry and described hereinbefore, particularly using DCC, DIC, HBTU, TBTU or BOP as reagents or using the mixed anhydride method.
If the starting compound XIV used is enantiomerically pure, partial racemisation of the C-terminal amino acid must be expected during the coupling step and possibly quantitative racemisation must be expected if triethylamine is used as the auxiliary base and dimethylformamide, dimethylacetamide or N-methyl-pyrrolidone is used as solvent.
h) In order to prepare compounds of general formula I wherein X denotes the oxygen atom:
Coupling carboxylic acids of general formula XVI, 
xe2x80x83wherein
R, Z, R11, m and n are as hereinbefore defined and
R2xe2x80x2 has the meanings given for R2 hereinbefore or denotes a group R2 substituted by the above-mentioned protecting groups,
to compounds of general formula XVII, 
xe2x80x83wherein
Axe2x80x2 has the meanings given for A hereinbefore or, if A denotes the divalent group of an amino acid, Axe2x80x2 optionally bears in the side chain a precursor group for the group R9, e.g. a cyanopropyl group, and
R3 and R4 are as hereinbefore defined,
and if necessary subsequently cleaving protecting groups or modifying precursor functions using the methods described above.
The coupling is carried out using the methods known from peptide chemistry and described above, particularly using DCC, DIC, HBTU, TBTU or BOP as reagents or using the mixed anhydride method.
If the starting compound XVI used is enantiomerically pure, during the coupling step partial racemisation must be expected or, if triethylamine is used as the auxiliary base and dimethylformamide, dimethylacetamide or N-methyl-pyrrolidone is used as solvent, quantitative racemisation must be expected based on the chiral centre of XVI.
i) In order to prepare compounds of general formula I wherein
R denotes an unbranched C1-6-alkylamino group optionally substituted at the nitrogen atom by a C1-6-alkyl group or by a phenylmethyl group, which may be substituted in the xcfx89-position
by a C4-10-cycloalkyl group,
by one or two phenyl groups, by a 1-naphthyl, 2-naphthyl or biphenylyl group,
by a 1H-indol-3-yl, 1,3-dihydro-2H-2-oxobenzimidazol-1-yl, 2,4(1H,3H)-dioxoquinazolin-1-yl, 2,4(1H,3H)-dioxoquinazolin-3-yl, 2,4(1H,3H)-dioxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,4-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxothieno[3,2-d]pyrimidin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-1-yl, 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 2(1H)-oxoquinolin-3-yl, 2(1H)-oxoquinoxalin-3-yl, 1,1-dioxido-3(4H)-oxo-1,2,4-benzothiadiazin-2-yl, 1,3-dihydro-4-(3-thienyl)-2H-2-oxoimidazol-1-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-5-phenyl-2H-2-oxoimidazol-1-yl, 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl, 3,4-dihydro-5-phenyl-2(1H)-oxopyrimidin-3-yl, 3,4-dihydro-6-phenyl-2(1H)-oxopyrimidin-3-yl- or 1,3-dihydro-2H-2-oxoimidazo[4,5-b]pyridin-3-yl-group,
by a 5-membered heteroaromatic ring linked via a carbon atom, which contains a nitrogen, oxygen or sulphur atom or, in addition to a nitrogen atom, contains an oxygen, sulphur or an additional nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl group, or
by a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic monocyclic rings via two adjacent carbon atoms in each case and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group,
whilst the phenyl, naphthyl and biphenylyl groups mentioned above for the substitution of the alkyl moiety of the alkylamino groups in the xcfx89-position and optionally partially hydrogenated mono- and bicyclic heteroaromatic rings in the carbon skeleton may additionally be mono-, di- or trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, C3-8-cycloalkyl groups, nitro, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, (4-morpholinyl)carbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the above-mentioned benzoyl, benzoylamino and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom or by an alkyl, trifluoromethyl, amino or acetylamino group,
or the group of formula 
xe2x80x83wherein
R5, R6, R7, RN, Y1, o and p are as hereinbefore defined and
Y2 denotes an N-atom,
Z represents the methylene group,
X denotes two hydrogen atoms,
A denotes a single bond,
m denotes the value 1 and
n denotes the value 0:
Coupling carboxylic acids of general formula XVIII, 
xe2x80x83wherein
R2, R3 and R4 are as hereinbefore defined,
with amines of general formula X,
Rxe2x80x94Hxe2x80x83xe2x80x83(X)
wherein R is as hereinbefore defined.
The coupling is carried out using the methods known from peptide chemistry and described above, particularly using DCC, DIC, HBTU, TBTU or BOP as reagents or using the mixed anhydride method.
j) In order to prepare compounds of general formula I wherein R3 and R4 have the meanings given hereinbefore with the exception of the hydrogen atoms, Z denotes a methylene group, X denotes two hydrogen atoms, A denotes a single bond, m is the number 1 and n is the number 0:
Reacting secondary amines of general formula XVa,
Hxe2x80x94NR3xe2x80x2R4xe2x80x2xe2x80x83xe2x80x83(XVa)
xe2x80x83wherein
R3xe2x80x2 and R4xe2x80x2 have the meanings given for R3 and R4 hereinbefore with the exception of hydrogen atoms,
with formaldehyde and CH-acid compounds of general formula XIX, 
wherein
R is as hereinbefore defined and
xe2x80x83R2 is as hereinbefore defined, but with the proviso that any acid functions present such as hydroxy groups are appropriately protected by suitable protecting groups.
The reaction is preferably carried out in a slightly acidic medium, using alcohols, e.g. methanol or ethanol, or lower aliphatic carboxylic acids, such as glacial acetic acid, as solvents and at temperatures between room temperature and the boiling point of the solvent in question. In a preferred variant, an inorganic acid salt such as the hydrochloride of a secondary amine of general formula XVa is heated with paraformaldehyde and a ketone of general formula XIX in glacial acetic acid to temperatures between 50xc2x0 C. and 80xc2x0 C.
k) In order to prepare compounds of general formula I wherein
R, R2, R3, R4, R11, X, Z, m and n are as hereinbefore defined and
A denotes the divalent group of formula III 
(linked to the NR3R4xe2x80x94 group via the xe2x80x94CXxe2x80x940 group)
xe2x80x83wherein
R8 denotes the hydrogen atom or an alkyl or phenylalkyl group and
R9 denotes an unbranched C1-5-alkyl group substituted in the xcfx89-position by an aminoiminomethylamino group:
Reacting compounds of general formula XX, 
xe2x80x83wherein
R, R2, R3, R4, R11, X, Z, m and n are as hereinbefore defined,
R8 denotes a hydrogen atom or an alkyl or phenylalkyl group and
R9 denotes an unbranched C1-5-alkyl group substituted in the xcfx89-position by a primary amino group,
with carbonic acid derivatives of general formula XXI, 
xe2x80x83wherein
Nu2 is a leaving group, e.g. an alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl group each having 1 to 10 carbon atoms in alkyl moiety, e.g. a methoxy, ethoxy, methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, propylsulphinyl, isopropylsulphinyl, methylsulphonyl or ethylsulphonyl group, the chlorine atom, the SO2H, SO3Hxe2x80x94 or OPOCl2xe2x80x94 group, or the group of general formula XXII, 
xe2x80x83wherein
R15 and R16, which may be identical or different, denote hydrogen atoms or C1-3-alkyl groups.
Occasionally, for example when Nu2 is an alkoxy group, instead of using the compounds of general formula XXI it is advantageous to use the inorganic acid salts thereof, e.g. the neutral sulphates or hydrochlorides thereof.
The reactions are carried out analogously to methods known from the literature (see G. B. L. Smith, J. Amer. Chem. Soc. 51, 476 [1929]; B. Rathke, Chem. Ber. 17, 297 [1884]; R. Phillips and H. T. Clarke, J. Amer. Chem. Soc. 45, 1755 [1923]; S. J. Angyal and W. K. Warburton, J. Amer. Chem. Soc. 73, 2492 [1951]; H. Lecher and F. Graf, Chem. Ber. 56, 1326 [1923]; J. Wityak, S. J. Gould, S. J. Hein and D. A. Keszler, J. Org. Chem. 52, 2179 [1987]; T. Teraji, Y. Nakai, G. J. Durant, WO-A-81/00109, Chem. Abstr. 94, 192336z [1981]; C. A. Maryanoff, R. C. Stanzione, J. N. Plampin and J. E. Mills, J. Org. Chem. 51, 1882-1884 [1986]; A. E. Miller and J. J. Bischoff, Synthesis 1986, 777; R. A. B. Bannard, A. A. Casselman, W. F. Cockburn and G. M. Brown, Can. J. Chem. 36, 1541 [1958]; Aktieselskabet Grea, Kopenhagen, DE 28 26 452-C2; K. Kim. Y-T. Lin and H. S. Mosher, Tetrah. Letters, 29, 3183-3186 [1988]; H. B. Arzeno et al., Synth. Commun. 20, 3433-3437 [1990]; H. Bredereck and K. Bredereck, Chem. Ber. 94, 2278 [1961]; H. Eilingsfeld, G. Neubauer, M. Seefelder and H. Weidinger, Chem. Ber. 97, 1232 [1964]; P. Pruszynski, Can. J. Chem. 65, 626 [1987]; D. F. Gavin, W. J. Schnabel, E. Kober and M. A. Robinson, J. Org. Chem. 32, 2511 [1967]; N. K. Hart, S. R. Johns, J. A. Lamberton and R. I. Willing, Aust. J. Chem. 23, 1679 [1970]; CIBA Ltd., Belgisches Patent 655 403; Chem. Abstr. 64, 17481 [1966]; R. A. B. Bannard, A. A. Casselman, W. F. Cockburn and G. M. Brown, Can. J. Chem. 36, 1541 [1958]; J. P. Greenstein, J. Org. Chem. 2, 480 [1937]; F. L. Scott and J. Reilly, J. Amer. Chem. Soc. 74, 4562 [1952]; W. R. Roush and A. E. Walts, J. Amer. Chem. Soc. 106, 721 [1984], M. S. Bernatowicz, Y. Wu and G. R. Matsueda, J. Org. Chem. 57, 2497-2502 [1992]; H. Tsunematsu, T. Imamura and S. Makisumi, J. Biochem. 94, 123-128 [1983]) at temperatures between 0xc2x0 C. and +100xc2x0 C., preferably between +40xc2x0 C. and +80xc2x0 C., using inert solvents, e.g. dichloromethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, dimethylformamide, dimethylacetamide, N-methyl-pyrrolidone or mixtures thereof and, depending on the nature of the Nu2xe2x80x94 group, frequently in the presence of auxiliary bases, especially alkali metal carbonates such as sodium- or potassium carbonate, or tertiary amines, preferably N-ethyl-diisopropylamine or triethylamine.
The amino acids of general formula I modified according to the invention contain at least one chiral centre. If the group A is also chiral, the compounds may occur in the form of two diastereomeric pairs of antipodes. The invention includes the individual isomers as well as the mixtures thereof.
The diastereomers are separated on the basis of their different physicochemical properties, e.g. by fractional crystallisation from suitable solvents, by high pressure liquid or column chromatography using chiral or preferably achiral stationary phases.
Racemates covered by general formula I may be separated, for example, by HPLC on suitable chiral stationary phases (e.g. Chiral AGP, Chiralpak AD). Racemates which contain a basic or acidic function can also be separated by means of the diastereomeric optically active salts which are formed on reacting with an optically active acid, e.g. (+)- or (xe2x88x92)-tartaric acid, (+)- or (xe2x88x92)-diacetyl tartaric acid, (+)- or (xe2x88x92)-monomethyltartrate or (+)-camphor sulphonic acid or an optically active base such as (R)-(+)-1-phenylethylamine, (S)-(xe2x88x92)-1-phenylethylamine or (S)-brucine.
According to a conventional process for separating isomers, the racemate of a compound of general formula I is reacted with one of the above-mentioned optically active acids or bases in equimolar amounts in a solvent and the crystalline, diastereomeric, optically active salts obtained are separated on the basis of their different solubilities. This reaction may be carried out in solvents of any kind provided that they are sufficiently different in terms of the solubility of the salts. Preferably, methanol, ethanol or mixtures thereof are used, e.g. in a ratio by volume of 50:50. Then each of the optically active salts is dissolved in water, neutralised with a base such as sodium carbonate or potassium carbonate, sodium hydroxide solution or potassium hydroxide solution, and in this way the corresponding free compound is obtained in the (+)- or (xe2x88x92)-form.
The (R)-enantiomer alone or a mixture of two optically active diastereomeric compounds coming within the scope of general formula I may also be obtained by carrying out the syntheses described above with a suitable reaction component in the (R)-configuration.
The starting materials of general formulae VII, IX, X, Xxe2x80x2, XI, XII, XIII, XV, XVa, XVII, XXI, XXII required to synthesis the compounds of general formula I as well as the amino acids used are commercially available or may be prepared by methods known from the literature.
Compounds of general formula VIII wherein Z denotes the group NR1 and those of general formula VIIIxe2x80x2 wherein X denotes the oxygen atom may be obtained from commonly available starting materials using methods familiar to peptide chemists.
Isocyanates of general formula XII can easily be obtained from xcex1-amino acid derivatives of general formula VIIIxe2x80x2 wherein R1 denotes a hydrogen atom and the other groups are as hereinbefore defined, or from the hydrochlorides thereof by reacting with phosgene, diphosgene or triphosgene in the presence of pyridine (see also: J. S. Nowick, N. A. Powell, T. M. Nguyen and G. Noronha, J. Org. Chem. 57, 7364-7366 [1992]).
Carboxylic acids of general formulae XIV and XVI may be obtained from the corresponding carboxylic acid esters by saponification, preferably in the presence of lithium hydroxide.
The carboxylic acids of general formula XVIII are obtained by saponifying corresponding carboxylic acid esters which are in turn prepared from suitable secondary amines, 4-aryl-4-oxobutanoic acid esters and formaldehyde by Mannich reaction.
Compounds of general formula XIX may be obtained from suitable 4-oxobutanoic acids and amines of general formula X using conventional methods.
The intermediate compounds of general formula XX come under general formula I and are thus within the scope of the present application. These compounds may be obtained, for example, using processes a) to h) described herein.
The compounds of general formula I may be converted into their physiologically acceptable salts with inorganic or organic acids, particularly for pharmaceutical applications. Examples of suitable acids for this purpose include hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulphuric acid, methanesulphonic acid, p-toluenesulphonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, mandelic acid, malic acid, citric acid, tartaric acid or maleic acid.
Moreover, if the new compounds of formula I thus obtained contain an acid function, for example a carboxy group, they may if desired be converted into the addition salts thereof with inorganic or organic bases, more particularly for pharmaceutical use, into the physiologically acceptable addition salts thereof. Bases which may be considered include, for example, sodium hydroxide, potassium hydroxide, ammonia, cyclohexylamine, dicyclohexylamine, ethanolamine, diethanolamine and triethanolamine.
The new compounds of general formula I and the physiologically acceptable salts thereof have CGRP-antagonistic properties and exhibit good affinities in CGRP-receptor binding studies. The compounds exhibit CGRP-antagonistic properties in the pharmacological test systems described hereinafter.
The following experiments were carried out to demonstrate the affinity of compounds of general formula I for human CGRP-receptors and their antagonistic properties:
A. Binding studies with SK-N-MC-cells expressing human CGRP-receptor
SK-N-MC-cells are cultivated in Dulbecco""s modified Eagle Medium. The medium of confluent cultures is removed. The cells are washed twice with PBS-buffer (Gibco 041-04190 M), detached by the addition of PBS-buffer mixed with 0.02% EDTA and isolated by centrifuging. After resuspension in 20 ml of Balanced Salts Solution [BSS (in mM): NaCl 120, KCl 5.4, NaHCO3 16.2, MgSO4 0.8, NaHPO4 1.0, CaCl2 1.8, D-Glucose 5.5, HEPES 30, pH7.40] the cells are centrifuged twice at 100xc3x97g and resuspended in BSS. After the cell number has been determined the cells are homogenised using an Ultra-Turrax and centrifuged for 10 minutes at 3000xc3x97g. The supernatent is discarded and the pellet is recentrifuged and resuspended (1 ml/1000000 cells) in Tris-buffer (10 mM Tris, 50 mM NaCl, 5 mM MgCl2, 1 mM EDTA, pH 7.40), enriched with 1% bovine serum albumin and 0.1% bacitracin. The homogenate is frozen at xe2x88x9280xc2x0 C. The membrane preparations are stable for more than 6 weeks under these conditions.
After thawing, the homogenate is diluted 1:10 with assay buffer (50 mM Tris, 150 mM NaCl, 5 mM MgCl2, 1 mM EDTA, pH 7.40) and homogenised for 30 seconds with an Ultra-Turrax. 230 xcexcl of the homogenate are incubated at ambient temperature for 180 minutes with 50 pM of 125I-Iodotyrosyl-Calcitonin-Gene-Related Peptide (Amersham) and increasing concentrations of the test substances in a total volume of 250 xcexcl. Incubation is ended by rapid filtration using GF/B-glass fibre filters treated with polyethyleneimine (0.1%) by means of a cell harvester. The protein-bound radioactivity is measured using a gammacounter. The non-specific binding is defined as the radioactivity bound after the presence of 1 xcexcM of human CGRP-alpha during incubation.
The concentration binding curves are analysed using a computer-aided non-linear curve adaptation.
The compounds of general formula I show IC50 valuesxe2x89xa610000 nM in the test described.
B. CGRP-Antagonism in SK-N-MC-cells
SK-N-MC-cells (1 million cells) are washed twice with 250 xcexcl of incubation buffer (Hanks"" HEPES, 1 mM 3-isobutyl-1-methylxanthine, 1% BSA, pH 7.4) and pre-incubated at 37xc2x0 C. for 15 minutes. After the addition of CGRP (10 xcexcl) as agonist in increasing concentrations (10xe2x88x9211 to 10xe2x88x926 M) or additionally of substance in 3 to 4 different concentrations, incubation is continued for a further 15 minutes.
Intracellular cAMP is then extracted by the addition of 20 xcexcl of 1M HCl and centrifugation (2000xc3x97g, 4xc2x0 C. for 15 minutes). The supernatants are frozen in liquid nitrogen and stored at xe2x88x9220xc2x0 C.
The cAMP contents of the samples are determined by radioimmunoassay (Amersham) and the pA2-values of antagonistically acting substances are determined graphically.
The compounds of general formula I display CGRP-antagonistic properties in a dosage range between 10xe2x88x9211 and 10xe2x88x925 M in the in vitro test model described.
In view of their pharmacological properties the compounds of general formula I and the salts thereof with physiologically acceptable acids or bases are thus suitable for acute and prophylactic treatment of headache, particularly migraine and cluster headaches. Moreover, the compounds of general formula I also have a beneficial effect on the following diseases: non-insulin-dependent diabetes mellitis (NIDDM), cardiovascular diseases, skin diseases, particularly thermal and radiation-induced skin damage including sunburn, inflammatory diseases, e.g. inflammatory joint diseases (arthritis), inflammatory lung diseases, allergic rhinitis, asthma, diseases which involve excessive vasodilation and resultant reductions in circulation, e.g. shock and sepsis, as well as morphine tolerance. In addition, the compounds of general formula I have the effect of alleviating pain in general.
The dosage needed to achieve such effects is appropriately 0.0001 to 3 mg/kg of body weight, preferably 0.01 to 1 mg/kg of body weight, by intravenous or subcutaneous route, and 0.01 to 10 mg/kg of body weight, preferably 0.1 to 10 mg/kg of body weight, when administered orally, nasally or by inhalation, in each case 1 to 3 times a day.
For this purpose, the compounds of general formula I prepared according to the invention may be formulated, optionally in combination with other active substances, such as antiemetics, prokinetics, neuroleptics, antidepressants, neurokinin-antagonists, anti-convulsants, histamine-H1-receptor antagonists, antimuscarinics, xcex2-blockers, xcex1-agonists and xcex1-antagonists, ergot alkaloids, mild analgesics, non-steroidal antiphlogistics, corticosteroids, calcium-antagonists, 5-HT1D-agonists or other antimigraine agents, together with one or more inert conventional carriers and/or diluents, e.g. corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethyleneglycol, propyleneglycol, cetylstearylalcohol, carboxymethylcellulose or fatty substances such as hard fat or suitable mixtures thereof, to produce conventional galenic preparations such as plain or coated tablets, capsules, powders, suspensions, solutions, metering aerosol or suppositories.
Thus, additional active substances which may be considered for the above-mentioned combinations include, for example, meloxicam, ergotamine, dihydroergotamine, metoclopramide, domperidon, diphenhydramine, cyclizine, promethazine, chlorpromazine, dexamethasone, flunarizine, dextropropoxyphene, meperidine, propranolol, nadolol, atenolol, clonidine, indoramine, carbamazepine, phenytoin, valproate, amitryptilin, lidocaine, diltiazem or sumatriptan and other 5-HT1D-agonists such as naratriptan, zolmitriptan, avitriptan, rizatriptan and eletriptan. The dosage for these active substances is appropriately 1/5 of the lowest dose normally recommended up to 1/1 of the normally recommended dosage, i.e. 20 to 100 mg of sumatriptan, for example.
The invention further relates to the use of the compounds of general formula I as valuable auxiliary agents for the production and purification (by affinity chromatography) of antibodies and, after suitable radiolabelling, e.g. by direct labelling with 125I or 131I or by tritiation of suitable precursors for example by replacing halogen atoms with tritium, in RIA- and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.